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-1.5478 -1.0755 TD [(vi)18.9(si)17.7(t.)-458.8(V)63.6(i)0(s)17.7(i)0(t)16.5(s)-468.6(w)12.4(e)0(r)13.5(e)-462.1(se)13.9(pa)20.8(ra)13.5(te)18.4(d)-461.7(b)0(y)]TJ /F9 1 Tf 12.9631 0 TD ($)Tj /F4 1 Tf 0.8251 0 TD [(2)-467.4(d)0(a)20.8(y)0(s)-458(a)0(n)15.1(d)-461.7(we)16.9(re)-458.8(pe)15.1(r)20.4(-)]TJ -13.7882 -1.0698 TD [(fo)19.6(rm)16.5(ed)-218.2(at)-214.9(th)18.9(e)-223.1(s)0(a)13.9(m)0(e)-215.6(t)0(i)16.5(m)0(e)-215.6(o)0(f)-213.7(d)0(a)15.1(y)73.2(.)-222.3(F)0(E)17.9(V)]TJ 7.97 0 0 7.97 200.239 593.178 Tm (1)Tj 9.963 0 0 9.963 206.476 593.178 Tm -0.0132 Tc [(wa)-13.2(s)-232.6(m)-13.2(e)4.5(a)-13.2(s)6.4(u)-13.2(re)-13.2(d)-225.7(a)-13.2(s)-226.9(t)-13.2(he)]TJ -14.8751 -1.0755 TD 0 Tc [(hi)18.9(gh)15.5(es)19.6(t)-344.6(o)0(f)-333.2(t)0(w)14.9(o)-336.5(su)14.3(cc)20.4(es)13.9(si)17.7(ve)-332(re)19.2(ad)15.1(in)18.8(gs)14.4(,)-341.8(w)12.4(it)16.5(hi)18.9(n)-342.2(1)0(0)15.5(0)-342.2(mL)19.7(,)-341.8(o)0(n)-337.3(a)]TJ T* 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[(br)19.6(ea)14.7(th)-516.1(ac)14.7(ti)16.5(va)20.8(te)18.4(d)-530(d)0(o)21.2(s)0(i)17.7(m)0(e)17.7(t)0(e)12.8(r)-525.9(\(M)17.7(EF)91.9(AR)12.6(,)-523.9(B)0(r)14.9(e)0(s)19.6(c)0(i)18.4(a)0(,)-519.4(I)0(t)17.3(a)0(l)18.4(y)0(\))-521(a)0(s)]TJ T* [(de)15.1(sc)19.6(ri)17.3(be)15.1(d)-319.4(p)0(r)13.9(e)0(v)20.8(i)0(o)18.9(u)0(s)14.4(l)0(y)-316.9([)0(6)19.6(])0(.)]TJ /F5 1 Tf 0 -4.046 TD [(Scr)30.3(ee)-8(ning)-335.5(visits)]TJ 0 -2.0998 TD [(V)69.1(isit)-381.3(1.)]TJ /F4 1 Tf 3.2436 0 TD [(In)-367.3(th)18.9(e)-371.1(f)0(i)17.3(r)0(s)18.4(t)-373(pa)15.1(rt)-364(of)-361.6(th)18.9(e)-371.1(s)0(t)17.7(u)0(d)15.5(y)73.2(,)-370.3(s)0(u)14.4(b)0(j)18.9(e)0(c)20.4(t)0(s)-363.6(u)0(n)15.5(d)0(e)20.8(r)0(w)15.7(e)0(n)15.1(t)]TJ -3.2436 -1.0755 TD [(an)-565.3(i)13.9(n)0(i)13.2(t)0(i)16.5(a)0(l)-562(M)0(B)14.6(S)-569(ch)20.8(al)12.8(le)18.4(ng)21.2(e)-575.9(t)0(o)-561.6(d)0(e)20.8(t)0(e)12.8(r)0(m)16.5(i)0(n)18.9(e)-570.2(th)18.9(ei)12.8(r)-571.4(P)11.4(D)]TJ 7.97 0 0 7.97 263.735 457.001 Tm (20)Tj 9.963 0 0 9.963 277.285 457.001 Tm (of)Tj -21.9826 -1.0755 TD [(MB)14.6(S)11.4(.)]TJ /F5 1 Tf 0 -3.1526 TD [(V)69.1(isit)-557.7(2.)]TJ /F4 1 Tf 3.5964 0 TD [(Su)16.3(bj)18.9(ec)14.7(ts)-540(re)19.2(tu)18.9(rn)13.9(ed)-536.8(fo)19.6(r)-548.7(a)-553.2(si)17.7(ng)21.2(le)-539.2(do)15.5(se)-538(ch)15.1(al)18.4(le)18.4(ng)15.5(e)]TJ -3.5964 -1.0698 TD [(wi)14.9(th)-442.1(th)13.2(e)-450.7(P)0(D)]TJ 7.97 0 0 7.97 108.964 404.22 Tm -0.0163 Tc (20)Tj 9.963 0 0 9.963 121.323 404.22 Tm 0 Tc [(of)-447(MB)14.6(S)-455.2(i)0(d)18.9(e)0(n)15.1(t)0(i)16.5(f)0(i)17.3(e)0(d)-445.8(a)0(t)-442.5(t)0(h)13.2(e)-450.7(pr)13.9(ev)20.8(io)13.2(us)-440.9(vi)13.2(si)17.7(t.)]TJ -6.3279 -1.0755 TD -0.0114 Tc [(FE)-11.4(V)]TJ 7.97 0 0 7.97 76.705 393.505 Tm 0 Tc (1)Tj 9.963 0 0 9.963 85.436 393.505 Tm [(wa)16.9(s)-480(m)0(e)17.7(a)0(s)13.9(u)0(r)19.6(e)0(d)-468.6(b)0(e)15.1(f)0(o)19.6(r)0(e)-470.2(\()0(b)19.6(a)0(s)13.9(e)0(l)18.4(i)0(n)18.9(e)0(\))-470.2(a)0(n)15.1(d)-473.1(2)-478.8(m)0(i)15.7(n)-478.8(af)19.2(te)12.8(r)]TJ -2.7258 -1.0755 TD [(in)18.9(ha)15.1(la)18.4(ti)16.5(on)-348.7(of)-350.2(3)-359.3(p)0(u)15.5(f)20.4(fs)-351.4(of)-350.2(no)15.5(rm)16.5(al)-351.4(sa)19.6(li)16.5(ne)-349.1(\(p)13.9(os)20(t-)17.3(sa)19.6(li)16.5(ne)-354.7(va)20.8(lu)18.9(e\))]TJ 0 -1.0698 TD [(an)15.1(d)-325.1(a)0(t)-323(1)0(,)-319.8(3)0(,)-314.1(5)0(,)-319.8(7)0(,)-319.8(1)0(0)15.5(,)-324.7(15)-320.2(an)15.1(d)-325.1(2)0(0)-320.2(m)0(i)15.7(n)-325.1(af)13.5(te)18.4(r)-326.7(t)0(h)13.2(e)-325.5(MB)14.6(S)-330(c)0(h)20.8(a)0(l)12.8(-)]TJ 0 -1.0755 TD [(le)18.4(ng)15.5(e.)-337.3(S)11.4(u)0(b)15.5(j)0(e)18.4(c)0(t)18.4(s)-349.1(we)16.9(re)-339.3(re)13.5(ch)20.8(al)12.8(l)13.9(e)0(n)15.1(g)0(e)15.1(d)-347.9(w)12.4(i)0(t)16.5(h)-347.9(th)18.9(e)-348.3(s)0(a)13.9(m)0(e)-340.8(d)0(o)21.2(s)0(e)-338.9(o)0(f)]TJ T* [(MB)14.6(S)-432.5(i)0(m)15.7(m)0(e)12(d)0(i)18.9(a)0(t)18.5(e)0(l)18.5(y)-438.9(af)19.2(te)18.4(r)-434.8(r)0(e)13.5(c)0(o)20.8(v)0(e)15.1(r)0(y)-424.2(\()0(F)14.7(E)0(V)]TJ 7.97 0 0 7.97 217.531 350.702 Tm (1)Tj /F8 1 Tf 9.963 0 0 9.963 225.865 350.702 Tm (>)Tj /F4 1 Tf 0.5463 0 TD [(95)21.2(%)-441.3(o)0(f)-424.2(p)0(o)15.5(s)0(t)17.7(-)]TJ -17.3676 -1.0755 TD [(sa)19.6(li)16.5(ne)-354.8(va)20.8(lu)18.9(e\))-356.3(an)20.8(d)-359.3(F)0(E)17.9(V)]TJ 7.97 0 0 7.97 148.195 339.987 Tm (1)Tj 9.963 0 0 9.963 155.792 339.987 Tm [(wa)16.9(s)-360.5(m)0(e)17.7(a)0(s)19.6(u)0(r)13.9(e)0(d)-349.1(a)0(t)-351.4(t)0(h)18.9(e)-365.4(sa)19.6(me)-352.2(in)18.9(te)18.5(r)14.7(-)]TJ -9.7877 -1.0698 TD [(va)15.1(ls)-369.3(fo)19.6(r)-377.9(a)-376.7(fu)13.9(rt)17.3(he)20.8(r)-377.9(2)0(0)-371.4(m)0(i)15.7(n)0(.)-365.3(S)0(u)16.3(b)0(j)18.9(e)0(c)14.7(t)0(s)-369.3(w)0(h)17.3(o)-376.3(ha)15.1(d)-376.3(a)-376.7(re)19.2(du)15.5(ct)18.4(io)18.9(n)]TJ 0 -1.0755 TD [(in)-334(AU)19.1(C)-346.9(o)0(f)-333.2(t)0(h)18.9(e)-342.6(ch)20.8(an)15.1(ge)15.1(s)-337.7(i)0(n)-334(F)0(E)17.9(V)]TJ 7.97 0 0 7.97 184.365 318.614 Tm (1)Tj 9.963 0 0 9.963 191.735 318.614 Tm [(ov)15.5(er)-333.6(20)-331.6(mi)15.7(n)-342.2(a)0(t)-334.4(t)0(h)18.8(e)-342.6(se)19.6(c-)]TJ -13.3956 -1.0755 TD [(on)15.5(d)-416.2(c)0(h)20.8(a)0(l)12.8(l)13.9(en)15.1(ge)-411.7(of)]TJ /F9 1 Tf 7.2668 0 TD ($)Tj /F4 1 Tf 0.8251 0 TD [(30)21.2(%)-418.5(w)0(e)16.9(r)0(e)-413.2(c)0(h)20.8(o)0(s)14.4(e)0(n)-406(t)0(o)-407.9(p)0(r)14(o)0(c)20.8(e)0(e)14.7(d)-416.2(to)-407.9(th)18.9(e)]TJ -8.092 -1.0755 TD [(se)19.6(co)15.1(nd)-314.5(pa)15.1(rt)-312.8(of)-316.1(th)18.9(e)-325.5(s)0(t)17.7(u)0(d)15.5(y)73.2(.)]TJ /F5 1 Tf 0 -3.4997 TD [(V)69.1(isit)-415.4(3)-416.2(and)-417.7(4:)-418.5(study)-417.5(of)-413.6(the)-420.5(effect)-422.7(of)-413.6(inhal)-8.6(ed)]TJ /F4 1 Tf 18.6707 0 TD (N)Tj /F5 1 Tf 7.472 0 0 6.641 251.433 266.74 Tm (G)Tj 9.963 0 0 9.963 256.819 262.318 Tm [(-mo)-7.8(no-)]TJ -19.9283 -1.0698 TD (methyl-)Tj 6.974 0 0 6.974 87.817 251.66 Tm (L)Tj 9.963 0 0 9.963 91.672 251.66 Tm [(-ar)29.1(gini)-7.8(ne)-605.1(o)-6.5(n)-604(the)-614(airway)-616.5(r)32.2(espons)-7.4(e)-610.1(t)0(o)-607.1(sodiu)-7.4(m)]TJ -3.3517 -1.0755 TD [(metabis)-9.9(ulphite.)]TJ /F4 1 Tf 6.7035 0 TD [(Af)15.7(te)18.4(r)-599.9(b)0(a)15.1(s)0(e)19.6(l)0(i)16.5(n)0(e)-593.8(m)0(e)17.7(a)0(s)19.6(u)0(r)14(e)0(m)17.7(e)0(n)15.1(t)-600.7(of)-589.3(FE)17.9(V)]TJ 7.97 0 0 7.97 279.042 240.945 Tm (1)Tj 9.963 0 0 9.963 282.954 240.945 Tm (,)Tj -22.5516 -1.0755 TD [(ea)14.7(ch)-479.9(su)14.4(bj)18.9(ec)20.4(t)-498.2(i)0(n)18.9(h)0(a)20.8(l)0(e)12.8(d)-490.2(an)-485.6(ae)20.4(ro)13.9(so)20(l)-492.5(o)0(f)-486.8(e)0(i)18.4(t)0(h)18.9(e)0(r)]TJ 6.974 0 0 6.974 233.405 230.23 Tm (L)Tj 9.963 0 0 9.963 237.543 230.23 Tm [(-N)15.7(MM)17.3(A)-494.1(\()0(2)]TJ -17.9935 -1.0755 TD [(mg)-482.7(in)-487.6(5)-490.2(m)0(L)-481.1(0)0(.)15.9(9)0(%)-481.9(s)0(a)13.9(l)0(i)16.5(n)0(e)20.8(\))-491.7(or)-486.8(pl)18.9(ac)20.4(eb)15.1(o)-490.2(\()0(5)-486.8(m)0(L)-481.1(o)0(f)-486.8(0)0(.)21.6(9)0(%)]TJ 0 -1.0698 TD [(sa)19.6(li)16.5(ne)15.1(\))-326.7(i)0(n)-322.6(a)-325.5(do)15.5(ub)21.2(le)18.4(-b)13.9(li)16.5(nd)21.2(,)-330.4(c)0(r)19.2(o)0(s)20(s)-332(ov)21.2(er)-322.2(st)17.7(ud)21.2(y)67.5(.)-324.7(Th)17.1(e)-325.5(d)0(r)13.9(u)0(g)-320.2(w)12.4(as)]TJ 0 -1.0755 TD [(ad)15.1(mi)21.4(ni)13.2(st)17.7(er)19.2(ed)]TJ /F5 1 Tf 5.406 0 TD [(vi)12.8(a)]TJ /F4 1 Tf 1.5934 0 TD [(a)-405.2(j)0(e)12.8(t)-401.5(ne)15.1(bu)21.2(li)16.5(ze)14.7(r)-406.4(\()0(P)20.4(a)0(r)19.2(i)-407.2(Ma)18.9(st)12(er)53.4(,)-404.4(S)0(t)13.9(a)0(r)19.2(n)0(b)15.5(e)0(r)30.6(g)0(,)]TJ -6.9994 -1.0755 TD [(Ge)16.9(rm)16.5(an)15.1(y\))-390.1(dr)14(iv)18.9(en)-388.9(by)-394.2(a)-405.2(c)0(o)20.8(m)0(p)18.1(r)0(e)13.5(s)0(s)18.9(e)0(d)-394.6(a)0(i)18.4(r)-400.7(so)20(ur)13.9(ce)-395(\(1)19.6(47)-394.2(kP)22(a\))]TJ T* [(wi)14.9(th)-396.6(an)-400.3(ou)21.2(tp)18.9(ut)-402.2(of)-395.8(0.)15.9(50)-394.2(g)]TJ /F10 1 Tf 10.2145 0.2049 TD (.)Tj /F4 1 Tf 0.2731 -0.2049 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 177.846 181.134 Tm (-1)Tj 9.963 0 0 9.963 183.798 176.712 Tm [(.)-410.1(T)12.2(he)-400.3(su)20(bj)18.9(ec)14.7(t)-407.2(i)0(n)18.9(h)0(a)15.1(l)0(e)18.4(d)-404.8(th)18.9(e)]TJ -12.5989 -1.0698 TD [(ae)14.7(ro)19.6(so)20(li)16.5(ze)14.7(d)-456(s)0(o)20(l)0(u)13.2(t)13.9(io)13.2(n)-456(a)0(t)-448.2(t)0(i)16.5(d)0(a)20.8(l)-458.4(br)13.9(ea)20.4(th)18.9(in)18.9(g)-461.7(t)0(h)18.9(r)0(o)19.6(u)0(g)15.5(h)-456(a)-456.4(m)0(o)18.1(u)0(t)13.2(h)]TJ 0 -1.0755 TD [(pi)18.9(ec)14.7(e)-354(u)0(n)21.2(t)0(i)16.5(l)-356(th)18.9(e)-354(n)0(e)20.8(b)0(u)15.5(l)0(i)16.5(z)0(e)20.4(r)-355.2(wa)16.9(s)-354.8(d)0(r)19.6(y)73.2(.)-353.2(F)0(E)17.9(V)]TJ 7.97 0 0 7.97 213.562 155.339 Tm (1)Tj 9.963 0 0 9.963 221.046 155.339 Tm [(wa)16.9(s)-354.8(m)0(e)17.7(a)0(s)14(u)0(r)19.6(e)0(d)-343.4(5)]TJ -16.3376 -1.0755 TD [(mi)15.7(n)-376.3(a)0(f)19.2(t)0(e)18.4(r)-377.9(fi)17.3(ni)18.9(sh)20(in)13.2(g)-370.7(t)0(h)13.2(e)-371.1(ae)14.7(ro)19.6(so)14.4(l)-373(d)0(e)15.1(l)0(i)16.5(v)0(e)20.8(r)0(y)76.5(,)-370.3(an)15.1(d)-376.3(t)0(h)18.8(e)-376.7(su)20(bj)18.9(ec)14.7(ts)]TJ T* [(in)18.9(ha)15.1(le)18.4(d)-581.2(3)-586.9(pu)21.2(f)20.4(f)0(s)-579.1(o)0(f)-572.2(n)0(o)15.5(r)0(m)16.5(a)0(l)-573.4(s)0(a)19.6(l)0(i)16.5(n)0(e)-576.7(a)0(n)20.8(d)-581.2(th)13.2(e)-581.6(F)11.4(EV)]TJ 7.97 0 0 7.97 260.447 133.909 Tm (1)Tj 9.963 0 0 9.963 270.198 133.909 Tm [(wa)11.2(s)]TJ -21.2713 -1.0698 TD [(me)17.7(as)14(ur)19.6(ed)-354.7(ag)15.1(ai)18.4(n.)-359.7(T)12.2(h)0(e)-360.4(s)0(u)20(b)0(j)18.9(e)0(c)14.7(t)0(s)-357.9(w)0(e)16.9(r)0(e)-356.3(t)0(h)18.9(e)0(n)-360.4(c)0(h)20.8(a)0(l)12.8(l)0(e)18.4(n)0(g)21.2(e)0(d)-360.4(w)0(i)14.9(t)13.9(h)]TJ 0 -1.0755 TD [(MB)14.6(S)-324.3(o)0(n)-314.5(t)0(w)14.9(o)-319.4(oc)15.1(ca)20.4(si)17.7(on)15.5(s)-326.3(a)0(s)-316.1(o)0(n)-314.5(v)0(i)18.9(s)0(i)17.7(t)-321.8(2.)]TJ /F5 1 Tf 25.1977 66.1583 TD [(Study)-826(of)-823.3(the)-818.8(effe)-8.6(ct)-818.1(of)-823.3(inhal)-8.6(ed)]TJ /F4 1 Tf 14.9946 0 TD (N)Tj /F5 1 Tf 7.472 0 0 6.641 465.902 776.069 Tm (G)Tj 9.963 0 0 9.963 471.288 771.647 Tm [(-mono-m)-10.7(ethyl-)]TJ 6.974 0 0 6.974 529.398 771.647 Tm (L)Tj 9.963 0 0 9.963 533.253 771.647 Tm (-)Tj -22.4777 -1.0471 TD [(ar)25.7(ginine)-339.8(on)-331.6(exh)-8.8(aled)-335.9(nitric)-337.7(oxide)-342.7(levels)]TJ /F4 1 Tf 1.0015 -2.0998 TD [(Ex)17.1(ha)15.1(le)18.4(d)-495.8(N)0(O)-493.1(w)0(a)16.9(s)-497(me)12(as)19.6(ur)19.6(ed)-491.3(us)20(in)13.2(g)-495.8(a)-496.3(hi)18.9(gh)15.5(ly)-487.6(se)13.9(ns)20(it)16.5(iv)18.9(e)]TJ -1.0015 -1.0528 TD [(ra)13.5(pi)18.9(d)-433.3(c)0(h)20.8(e)0(m)12(i)0(l)16.5(u)0(m)18.1(i)0(n)18.9(e)0(s)19.6(e)0(n)15.1(c)0(e)-423.4(a)0(n)15.1(a)0(l)18.5(y)0(z)20.8(e)0(r)-424.6(\()0(L)15.5(R)0(2)16.5(0)0(0)15.5(0)0(,)-422.2(v)0(e)20.8(r)0(s)18.4(i)0(o)13.2(n)-433.2(2.)21.6(2;)]TJ 0 -1.0471 TD [(Lo)17.1(ga)15.1(n)-336.5(R)11.6(es)13.9(ea)20.4(rc)13.5(h,)-325.5(Ro)16.5(ch)20.8(es)13.9(te)18.4(r)37.5(,)-336.1(U)12.4(K)0(\))-331.4(a)0(s)-327.5(p)0(r)19.6(e)0(v)15.1(i)0(o)18.9(u)0(s)14.4(l)0(y)-322.6(d)0(e)15.1(s)0(c)19.6(r)0(i)17.3(b)0(e)15.1(d)]TJ 0 -1.0528 TD [([7)13.9(].)-253.1(Thr)-8(ee)-252.7(healt)-9.4(hy)-257.6(nonsmokin)-7.9(g)-256.8(control)-262.5(subjects)-264.4(without)-261.1(a)]TJ 0 -1.0471 TD [(hist)-9(ory)-510.3(of)-509.6(asthma)-518.6(and/or)-509.7(whee)-7.8(ze)-508.8(wer)-8.2(e)-507.6(recrui)-11(ted)-511.5(from)]TJ 0 -1.0527 TD [(hospi)-7.4(tal)-269.2(staff)-261.4(and)-270.1(their)-272.3(exhale)-8.2(d)-268.2(N)0(O)-265.5(level)-9.4(s)-263.7(wer)-8.2(e)-262.9(meas)-8.2(ured)]TJ T* [(before)-247.6(\(baseline\))-245.6(a)-6.9(n)0(d)-234.8(1)0(,)-240.2(15,)-235.2(an)-7.6(d)-234.1(6)0(0)-240.5(min)-241.1(after)-243.5(inhalati)-10.7(on)-234.8(of)]TJ 6.974 0 0 6.974 309.316 667.049 Tm (L)Tj 9.963 0 0 9.963 313.568 667.049 Tm [(-NMMA)-341.5(\(2)-338.9(mg)-334.7(in)-334(5)-336.5(m)0(L)-333.2(0.9%)-340.8(saline\).)]TJ /F5 1 Tf -0.4268 -2.9022 TD [(Ana)-6.4(lyses)]TJ /F4 1 Tf 1.0015 -1.9519 TD [(So)16.3(di)18.9(um)-391.6(me)17.7(ta)18.4(bi)18.9(su)14.4(lp)18.9(hi)18.9(te)-391.3(P)11.4(D)]TJ 7.97 0 0 7.97 426.898 618.69 Tm (20)Tj 9.963 0 0 9.963 438.69 618.69 Tm [(wa)11.2(s)-394.6(c)0(a)20.4(l)0(c)12.8(u)0(l)18.9(a)0(t)18.4(e)0(d)-388.9(b)0(y)-382.8(l)0(i)16.5(n)0(e)15.1(a)0(r)]TJ -12.9858 -1.0471 TD [(in)13.2(te)18.4(rp)19.6(ol)18.9(at)12.8(io)18.9(n)-359.3(o)0(f)-355.9(t)0(h)18.8(e)-359.7(lo)13.2(g)-359.3(d)0(o)21.2(s)0(e)13.9(-)0(r)18(e)0(s)19.6(p)0(o)15.5(n)0(s)20(e)-365.4(cu)20.8(rv)13.9(e.)-348.7(Th)17.1(e)-365.4(a)0(i)18.4(r)0(w)15.7(a)0(y)]TJ 0 -1.0527 TD [(re)13.5(sp)20(on)15.5(se)-190.9(to)-197.4(si)17.7(ng)21.2(le)-197.8(do)21.2(se)-196.6(ch)15.1(al)18.5(le)18.4(ng)15.5(e)-200.3(w)0(i)14.9(t)0(h)-191.7(M)0(B)14.6(S)-204.8(wa)16.9(s)-201.1(e)0(x)15.1(p)0(r)19.6(e)0(s)13.9(s)0(e)19.6(d)]TJ 0 -1.0471 TD [(as)-270.6(ma)12(xi)18.9(mu)18.1(m)-282.7(f)0(a)19.2(l)0(l)-273.7(i)0(n)-271.4(F)11.4(EV)]TJ 7.97 0 0 7.97 406.828 587.338 Tm (1)Tj 9.963 0 0 9.963 410.683 587.338 Tm [(%)-282(a)0(n)15.1(d)-279.6(A)12.4(U)0(C)-271.9(i)0(n)-271.4(l)0(i)16.5(t)0(r)17.3(e)0(s)-270.6(p)0(e)15.1(r)-281.2(mi)15.7(nu)21.2(te)]TJ -10.1747 -1.0527 TD [(fo)13.9(r)-395(c)0(h)15.1(a)0(n)20.8(g)0(e)-388.9(f)0(r)18(o)0(m)-391.6(p)0(o)21.2(s)0(t)17.7(-)0(s)18.4(a)0(l)12.8(i)0(n)18.9(e)-393.8(FE)17.9(V)]TJ 7.97 0 0 7.97 442.885 576.85 Tm (1)Tj /F8 1 Tf 9.963 0 0 9.963 450.822 576.85 Tm (>)Tj /F4 1 Tf 0.5406 0 TD [(20)-388.5(mi)15.7(n.)-388.1(An)-386.7(RI)-389.1(wa)16.9(s)]TJ -14.7442 -1.0527 TD [(de)15.1(ri)17.3(ve)15.1(d)-245.5(b)0(y)-240.5(e)0(x)15.1(p)0(r)19.6(e)0(s)13.9(s)0(i)17.7(n)0(g)-240.5(t)0(h)18.8(e)-251.6(di)18.9(f)20.4(f)0(e)13.5(r)0(e)19.2(n)0(c)15.1(e)-245.9(be)15.1(tw)14.9(ee)20.4(n)-251.2(A)0(U)13.4(C)-250.2(fo)19.6(r)-252.8(t)0(h)18.9(e)]TJ 0 -1.0471 TD [(fi)17.3(rs)12.8(t)-264.9(a)0(n)20.8(d)-268.2(se)19.6(co)15.1(nd)-257.6(ch)20.8(al)12.8(le)18.4(ng)21.2(e)-268.6(a)0(s)-259.2(a)-262.9(pe)15.1(rc)19.2(en)15.1(ta)18.4(ge)-258(of)-259.2(th)18.8(e)-262.9(v)0(a)15.1(l)0(u)18.8(e)0(s)-259.2(o)0(f)]TJ 0 -1.0527 TD [(th)13.2(e)-382.4(f)0(i)17.3(r)0(s)12.8(t)-384.4(ch)15.1(al)18.5(le)18.4(ng)15.5(e.)-377.1(B)11.6(a)0(s)13.9(e)0(l)18.5(i)0(n)18.9(e)-388.1(F)11.4(E)0(V)]TJ 7.97 0 0 7.97 443.055 545.442 Tm (1)Tj 9.963 0 0 9.963 446.91 545.442 Tm [(,)-387.3(t)0(h)18.9(e)-388.1(ma)17.7(xi)13.2(mu)18.1(m)-385.2(f)0(a)13.5(l)0(l)-376.2(i)0(n)]TJ -13.811 -1.0471 TD [(FE)17.9(V)]TJ 7.97 0 0 7.97 327.742 535.011 Tm (1)Tj 9.963 0 0 9.963 331.653 535.011 Tm [(%)-344.6(a)0(n)15.1(d)-342.2(AU)13.4(C)-346.9(f)0(o)19.6(r)-349.5(t)13.9(h)0(e)-337.7(f)0(i)17.3(r)0(s)18.4(t)-350.3(an)20.8(d)-347.9(s)0(e)19.6(c)0(o)15.1(n)0(d)-331.6(c)0(h)15.1(a)0(l)18.5(l)0(e)18.4(n)0(g)15.5(e)-342.6(an)15.1(d)]TJ -2.2421 -1.0527 TD -0.0193 Tc [(t)-19.3(h)-6.1(e)-231(R)-7.7(I)-232.2(w)-19.3(er)-19.3(e)-222(c)-19.3(om)-19.3(p)-6.9(a)-19.3(re)-19.3(d)-220.4(w)-19.3(i)-4.4(t)-19.3(hi)-19.3(n)-222.4(s)-19.3(ub)-19.3(j)-6.1(e)-19.3(ct)-19.3(s)-223.6(b)-19.3(y)-220(s)-19.3(tu)-19.3(d)-3.8(e)-19.3(nt)]TJ /F11 1 Tf 18.7788 0 TD 0 Tc (')Tj /F4 1 Tf 0.2105 0 TD 0.2125 Tc [(sp)212.5(a)233.3(i)212.5(r)229.8(e)212.5(d)11.4(t)212.5(-)]TJ -18.9894 -1.0471 TD 0 Tc [(te)12.8(st)17.7(.)-376(M)0(a)18.9(x)0(i)13.2(m)0(u)18.1(m)-379.5(fa)19.2(ll)-370.5(in)-373.8(F)11.4(E)0(V)]TJ 7.97 0 0 7.97 419.527 514.091 Tm (1)Tj 9.963 0 0 9.963 423.383 514.091 Tm [(,)-381.6(A)12.4(UC)-374.4(an)15.1(d)-376.3(R)0(I)-372(f)0(o)19.6(r)-377.9(dr)13.9(ug)-365.7(an)15.1(d)]TJ -11.4494 -1.0527 TD [(pl)13.2(ac)20.4(eb)15.1(o)-313.7(a)0(r)19.2(e)-314.1(pr)13.9(es)19.6(en)20.8(te)12.8(d)-313.7(a)0(s)-304.7(m)0(e)17.7(a)0(n)15.1(\213)]TJ 6.974 0 0 6.974 435.231 503.603 Tm 0.0001 Tc [(SE)18(M)]TJ 9.963 0 0 9.963 452.523 503.603 Tm 0 Tc [(wi)14.9(th)-305.5(95)21.2(%)-316.1(c)0(o)15.1(n)0(f)19.6(i)0(d)18.9(e)0(n)15.1(c)0(e)]TJ -14.3743 -1.0471 TD [(in)13.2(te)18.4(rv)19.6(al)-266.1(\(C)14.9(I\))-260.8(of)-264.9(th)18.8(e)-274.3(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nc)15.1(e)-268.6(b)0(e)15.1(t)0(w)20.6(e)0(e)14.7(n)-273.9(th)18.8(e)-274.3(t)0(w)20.6(o)-273.9(tr)17.3(ea)14.7(t)13.9(m)0(e)12(n)0(t)18.9(s)0(.)]TJ 1.0015 -1.0528 TD [(It)-341.2(wa)11.2(s)-349.1(c)0(a)20.4(l)0(c)18.4(u)0(l)13.2(a)0(t)18.5(e)0(d)-337.7(t)0(h)18.9(a)0(t)-345.7(w)12.4(it)16.5(h)]TJ /F9 1 Tf 10.96 0 TD ($)Tj /F4 1 Tf 0.8251 0 TD -0.0175 Tc [(9)-365.4(s)-17.5(u)2.5(b)-17.5(je)-17.5(ct)-17.5(s)-358.3(r)-17.5(ec)-17.5(ei)-17.5(vi)-17.5(ng)-365.4(b)-17.5(o)-2(t)-17.5(h)]TJ -12.7867 -1.0471 TD 0 Tc [(tr)17.3(ea)14.7(tm)15.7(en)20.8(ts)17.7(,)-353.2(t)0(h)18.9(e)-354(st)17.7(ud)15.5(y)-353.6(w)12.4(ou)15.5(ld)-345.3(ha)20.8(ve)-343.4(95)15.5(%)-355.9(p)0(o)21.2(w)0(e)16.9(r)-355.2(to)-345.3(de)20.8(te)18.4(ct)-345.8(a)]TJ 0 -1.0527 TD [(ch)15.1(an)15.1(ge)-377.5(in)-385.2(R)11.6(I)-395(be)20.8(tw)14.9(ee)14.7(n)-387.7(t)0(w)14.9(o)-387.7(tr)17.3(ea)14.7(tm)15.7(en)20.8(ts)-386.4(of)-378.7(15)15.5(%)-390.1(\()0(g)13.9(i)0(v)18.8(e)0(n)-383.2(a)0(n)]TJ 0 -1.0471 TD [(in)13.2(te)18.4(r)20.4(-)0(s)18.4(u)0(b)15.5(j)0(e)18.4(c)0(t)-243.3(s)0(t)12(a)0(n)20.8(d)0(a)15.1(r)0(d)-242.1(d)0(e)15.1(v)0(i)18.9(a)0(t)18.5(i)0(o)18.8(n)-256.8(fo)19.6(r)-258.4(r)0(e)19.2(p)0(e)20.8(a)0(t)-249(e)0(s)19.6(t)0(i)16.5(m)0(a)17.7(t)0(i)16.5(o)0(n)-246.2(o)0(f)-247.8(R)11.6(I)]TJ 0 -1.0528 TD [(of)-316.1(12)15.5(%)-327.5([)0(3)19.6(]\).)]TJ /F7 1 Tf 9.8617 -3.0501 TD [(Res)-7.8(ults)]TJ /F5 1 Tf -9.8617 -1.8494 TD [(Bas)-7.6(eline)-339.4(data)-335.5(fr)29(om)-335.5(scr)29.1(eening)-343.5(visits)]TJ /F4 1 Tf 1.0015 -2.0998 TD [(Ch)16.5(al)12.8(le)18.4(ng)21.2(e)-433.7(w)0(i)14.9(t)0(h)-419.3(t)0(h)13.2(e)-428(tw)14.9(o)-433.2(s)0(i)17.7(n)0(g)21.2(l)0(e)-425.4(d)0(o)21.2(s)0(e)14(s)-428.8(of)-424.2(MB)14.6(S)-432.5(o)0(n)-422.6(t)0(h)18.9(e)]TJ -1.0015 -1.0527 TD [(se)13.9(co)20.8(nd)-428.3(sc)13.9(re)19.2(en)15.1(i)13.9(n)0(g)-428.3(v)0(i)13.2(s)0(i)17.7(t)-435.6(ca)20.4(us)14.4(ed)-428.7(a)-433.7(m)0(e)12(a)0(n)-423(m)0(a)12(x)0(i)18.9(m)0(u)18.1(m)-436.4(fa)13.5(ll)-427.4(in)]TJ 0 -1.0471 TD [(FE)17.9(V)]TJ 7.97 0 0 7.97 327.742 350.192 Tm (1)Tj 9.963 0 0 9.963 336.302 350.192 Tm [(of)-447(26)21.2(\2132)16.7(.6)15.9(%)-458.4(a)0(n)20.8(d)-461.7(16)21.2(\2132)16.7(.4)15.9(%)-452.7(a)0(f)13.5(t)0(e)18.5(r)-457.6(th)18.9(e)-456.4(f)0(i)17.3(r)0(s)18.4(t)-458.4(an)15.1(d)-456(t)0(h)18.9(e)]TJ -2.7087 -1.0528 TD [(se)13.9(co)20.8(nd)-764.1(ch)15.1(al)18.4(le)18.4(ng)15.5(e,)-764.1(re)19.2(sp)14.3(ec)20.4(ti)16.5(ve)15.1(l)13.9(y)-774.7(\(9)13.9(5%)-760.7(CI)-764.7(6.)15.9(5\261)15.5(13)21.2(.3)15.9(%,)]TJ 0 -1.0471 TD (p)Tj /F8 1 Tf 0.4951 0 TD (<)Tj /F4 1 Tf 0.5406 0 TD [(0.)15.9(00)21.2(01)15.5(\).)-361.2(Th)17.1(e)-371.1(A)0(U)13.4(C)-369.7(wa)16.9(s)-371.8(1)39.1(1\213)16.7(2.)21.6(7)-370.7(a)0(n)15.1(d)-370.7(6\213)16.7(2)-370.7(L)]TJ /F10 1 Tf 17.2481 0.1992 TD (.)Tj /F4 1 Tf 0.2675 -0.1992 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 509.272 333.694 Tm (-1)Tj 9.963 0 0 9.963 519.023 329.272 Tm [(af)19.2(te)18.4(r)]TJ -21.0493 -1.0528 TD [(th)13.2(e)-223.1(f)0(i)17.3(r)0(s)18.5(t)-230.8(an)20.8(d)-228.4(t)0(h)18.8(e)-223.1(se)13.9(co)20.8(nd)-217.8(ch)15.1(al)18.4(le)18.4(ng)15.5(e,)-212.1(re)13.5(sp)20(ec)14.7(ti)16.5(ve)20.8(ly)-220.2(\(9)19.6(5%)-220.1(C)11.6(I)-230(3\261)]TJ 0 -1.0471 TD [(6.)15.9(9,)-314.1(p)]TJ /F8 1 Tf 2.2876 0 TD (<)Tj /F4 1 Tf 0.5463 0 TD [(0.)21.6(00)15.5(01)21.2(\).)-315.7(Th)17.1(e)-325.5(m)0(e)17.7(a)0(n)-314.9(R)0(I)-320.8(w)12.4(as)-316.1(55)15.5(\213)11.8(5)0(.)15.9(6)0(%)18.9(.)]TJ /F5 1 Tf -2.8339 -3.0046 TD 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[(EFFECT)-325.2(OF)-330.8(L-N)-9.9(MMA)-334.3(ON)-331.7(MBS)-339.9(RESPONSE)-337.2(I)0.1(N)-340.8(A)0(STHMA)]TJ ET endstream endobj 17 0 obj << /ProcSet [/PDF /Text ] /Font << /F4 7 0 R /F5 8 0 R /F7 10 0 R /F8 11 0 R /F9 12 0 R /F10 18 0 R /F11 19 0 R >> /ExtGState << /GS2 13 0 R >> >> endobj 21 0 obj << /Length 26779 >> stream BT /F4 1 Tf 9.963 0 0 9.963 58.28 621.921 Tm 0 g /GS2 gs 0 Tc [(15)15.5(\213)11.8(1)0(.)15.9(3)0(%)-373.8(a)0(n)15.1(d)-387.7(15)21.2(\2132)16.7(.1)15.9(%)-384.4(r)0(e)19.2(s)0(p)14.4(e)0(c)20.4(t)0(i)16.5(v)0(e)15.1(l)0(y)81.4(,)-381.7(95)15.5(%)-384.4(C)0(I)-377.7(-)0(6)13.9(.)0(1)21.6(\261)0(4)15.5(.)0(6)21.6(%)0(,)]TJ 0 -1.0528 TD 0 Tw (p)Tj /F8 1 Tf 0.4894 0 TD (=)Tj /F4 1 Tf 0.5463 0 TD [(0.)21.6(7,)-348.3(AU)19.1(C)-358.3(w)0(a)16.9(s)-354.8(4.)21.6(94)15.5(\2130)16.7(.9)-342.6(L)]TJ /F10 1 Tf 10.573 0.2049 TD (.)Tj /F4 1 Tf 0.2731 -0.2049 TD [(mi)15.7(n)]TJ 7.472 0 0 6.641 191.735 615.855 Tm (-1)Tj 9.963 0 0 9.963 201.316 611.433 Tm 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[(6.)15.9(9%)-436.4(an)20.8(d)-444.6(5)0(0)15.5(\213)0(7)16.7(.)0(3)21.6(%)-447(re)13.5(sp)20(ec)14.7(ti)16.5(ve)20.8(ly)81.4(,)-444.2(9)0(5)15.5(%)-447(CI)-440.3(fo)19.6(r)-446.2(d)0(i)18.9(f)20.4(fe)13.5(re)19.2(nc)15.1(e)]TJ 0 -1.0528 TD [(-2)19.6(0\261)15.5(18)15.5(,)-319.1(p)]TJ /F8 1 Tf 3.8354 0 TD (=)Tj /F4 1 Tf 0.5406 0 TD [(0.)15.9(89)21.2(\))-326.7(\()0(t)17.3(a)0(b)20.8(l)0(e)-317.3(1)-325.1(and)-332.7(fig.)-342.4(1\).)]TJ /F5 1 Tf -4.376 -2.5152 TD [(The)-656.3(effe)-8.6(ct)-658.7(of)-652.6(inhal)-8.6(ed)]TJ /F4 1 Tf 9.9983 0 TD (N)Tj /F5 1 Tf 7.472 0 0 6.641 165.033 548.957 Tm (G)Tj 9.963 0 0 9.963 170.419 544.535 Tm [(-mo)-7.8(no-methyl)-12.3(-)]TJ 6.974 0 0 6.974 228.586 544.535 Tm (L)Tj 9.963 0 0 9.963 232.441 544.535 Tm [(-ar)29.1(ginine)-658.5(on)]TJ -17.4814 -1.0527 TD [(exhale)-8.2(d)-330.8(nitr)-9(ic)-334.4(oxide)-337.1(level)-9.8(s)]TJ /F4 1 Tf 1.0015 -1.7527 TD 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[(0.05)-332.7(at)-334.4(all)-337.5(time)-341.4(points\).)]TJ /F7 1 Tf 25.744 14.7727 TD [(Discu)-10.9(ssion)]TJ /F4 1 Tf -8.1659 -2.0998 TD [(Th)17.1(e)-143.4(a)0(i)18.4(m)-140.5(of)-134(th)18.8(is)-130.3(st)17.7(ud)15.5(y)-137.3(w)0(a)16.9(s)-144.2(to)-129.1(de)15.1(t)13.9(e)0(r)13.5(m)0(i)15.7(n)0(e)-127.1(w)0(h)11.6(e)0(t)18.5(h)0(e)20.8(r)-144.6(th)18.8(e)-137.7(\()0(N)15.7(O)0(S)18.1(\))]TJ -1.0015 -1.0641 TD [(in)13.2(hi)18.9(bi)18.9(to)18.8(r)37.5(,)]TJ 6.974 0 0 6.974 348.775 590.4 Tm (L)Tj 9.963 0 0 9.963 352.913 590.4 Tm [(-N)15.7(MM)11.6(A)12.4(,)-421.5(wo)17.3(ul)18.9(d)-416.2(i)0(n)13.2(h)0(i)18.9(b)0(i)18.9(t)-418.6(MB)14.6(S)11.4(-)0(i)17.3(n)0(d)15.5(u)0(c)20.8(e)0(d)-411.7(r)0(e)19.2(f)0(r)12.4(a)0(c)20.4(-)]TJ -4.376 -1.0641 TD [(to)13.2(ri)17.3(ne)20.8(ss)18.9(,)-250.8(t)0(h)18.8(u)0(s)-241.7(i)0(m)15.7(p)0(l)18.9(i)0(c)18.4(a)0(t)12.8(i)0(n)18.9(g)-251.2(N)12.4(O)-255.1(i)13.9(n)-251.1(th)18.8(e)-251.6(r)0(e)19.2(f)0(r)12.4(a)0(c)20.4(t)0(o)18.8(r)0(i)17.3(n)0(e)15.1(s)0(s)-242.9(p)0(r)19.6(o)0(c)15.1(e)0(s)19.6(s)0(.)]TJ T* [(It)-523.3(wa)16.9(s)-531.2(h)0(y)21.2(p)0(o)15.5(t)0(h)18.9(e)0(s)13.9(i)0(z)18.4(e)0(d)-519.8(t)0(h)18.9(a)0(t)-522.2(r)0(e)19.2(l)0(e)12.8(a)0(s)19.6(e)-530.4(of)-521(NO)-521.5(fr)18(om)-522.5(iN)14.9(AN)13.4(C)]TJ T* [(ne)15.1(rv)19.6(es)-367.3(du)15.5(ri)17.3(ng)-365.7(a)-371.1(f)0(i)17.3(r)0(s)12.8(t)-373(br)19.6(on)15.5(ch)20.8(oc)15.1(on)21.2(st)12(ri)17.3(ct)18.4(or)-367.3(ch)20.8(al)18.5(le)18.5(ng)15.5(e)-376.7(w)0(o)17.3(u)0(l)18.8(d)]TJ 0 -1.0698 TD [(pr)13.9(ot)18.9(ec)14.7(t)-327.5(a)0(g)20.8(a)0(i)18.4(n)0(s)14.4(t)-327.5(a)-325.5(s)0(e)19.6(c)0(o)15.1(n)0(d)-320.2(c)0(h)20.8(a)0(l)18.5(l)0(e)12.8(n)0(g)21.2(e)0(.)-320.2(A)0(l)14.9(t)13.9(ho)15.5(ug)15.5(h)-325.1(e)0(v)15.1(i)13.9(de)15.1(nc)15.1(e)-325.5(o)0(f)]TJ 0 -1.0641 TD [(re)13.5(fr)18(ac)14.7(t)13.9(o)0(r)13.9(i)0(n)18.8(e)0(s)19.6(s)-514.1(t)13.9(o)-512.9(MB)14.6(S)11.4(-)0(i)17.3(n)0(d)15.5(u)0(c)20.8(e)0(d)-502.7(b)0(r)19.6(o)0(n)15.5(c)0(h)20.8(o)0(c)15.1(o)0(n)21.2(s)0(t)17.7(r)0(i)17.3(c)0(t)12.8(i)0(o)18.9(n)-507.2(wa)16.9(s)]TJ T* [(sh)14.4(ow)17.3(n,)]TJ 6.974 0 0 6.974 342.765 526.734 Tm (L)Tj 9.963 0 0 9.963 346.904 526.734 Tm [(-N)15.7(MM)11.6(A)-545.3(h)0(a)15.1(d)-547.1(no)-536.4(ef)24.9(fe)19.2(ct)-539.2(on)-536.4(th)18.8(e)-547.5(M)0(B)14.6(S)0(-)14.7(i)0(n)18.9(d)0(u)21.2(c)0(e)14.7(d)]TJ -3.7728 -1.0641 TD [(re)13.5(fr)18(ac)14.7(t)13.9(o)0(r)13.9(i)0(n)18.8(e)0(s)19.6(s)0(.)]TJ 1.0015 -1.0471 TD [(Th)17.1(e)-416.6(s)0(t)17.7(u)0(d)21.2(y)-416.2(wa)16.9(s)-411.7(c)0(a)14.7(r)0(e)19.2(f)0(u)13.9(l)0(l)16.5(y)-410.5(de)15.1(si)17.7(gn)21.2(ed)-406(to)-402.2(tr)17.3(y)-416.2(t)0(o)-402.2(m)0(a)12(x)0(i)18.9(m)0(i)15.7(z)0(e)]TJ -1.0015 -1.0641 TD [(th)13.2(e)-342.6(c)0(h)15.1(a)0(n)20.8(c)0(e)-338.1(o)0(f)-333.2(s)0(e)19.6(e)0(i)12.8(n)0(g)-331.6(a)0(n)-337.7(e)0(f)30.6(f)0(e)13.5(c)0(t)18.5(.)-341.8(Su)16.3(bj)18.8(ec)14.7(ts)-335.2(we)16.9(re)-333.6(re)13.5(qu)21.2(ir)17.3(ed)-337.7(to)]TJ T* [(sh)14.4(ow)-307.1(a)-319.8(s)0(i)17.7(g)0(n)15.5(i)0(f)17.3(i)0(c)18.4(a)0(n)15.1(t)-316.1(de)15.1(gr)19.6(ee)-309.6(of)-310.4(MB)14.6(S)-318.7(r)0(e)19.2(f)0(r)18(a)0(c)14.7(t)0(o)18.8(r)0(i)17.3(n)0(e)15.1(s)0(s)-305.5(\()]TJ /F9 1 Tf 19.86 0 TD ($)Tj /F4 1 Tf 0.8251 0 TD [(30)21.2(%\))]TJ -20.6851 -1.0641 TD [(be)15.1(fo)19.6(re)-453.1(en)20.8(tr)17.3(y)-461.7(i)0(n)18.9(t)0(o)-447.8(t)0(h)18.9(e)-462.1(do)21.2(ub)15.5(le)18.4(-b)13.9(l)13.9(i)0(n)13.2(d)-456(ph)15.5(as)19.6(e.)-451.1(A)-454.3(d)0(o)15.5(s)0(e)-452.7(o)0(f)]TJ 6.974 0 0 6.974 529.115 473.896 Tm (L)Tj 9.963 0 0 9.963 533.253 473.896 Tm (-)Tj -22.4777 -1.0698 TD [(NM)15.3(MA)-235(w)12.4(h)0(i)13.2(c)0(h)-309.2(w)0(a)16.9(s)-320.6(tw)14.9(ic)18.4(e)-319.8(a)0(s)-316.1(h)0(i)18.9(g)0(h)-308.8(a)0(s)-316.1(t)0(h)18.8(e)-319.8(do)15.5(se)-310.4(wi)14.9(th)-311.2(wh)17.3(ic)18.4(h)]TJ 0 -1.0641 TD (R)Tj 6.974 0 0 6.974 315.893 452.636 Tm 0.0001 Tc [(IC)20.7(CIA)23.4(R)0(D)18.4(OLO)]TJ /F5 1 Tf 9.963 0 0 9.963 361.134 452.636 Tm 0 Tc [(et)-294.5(al)18.9(.)]TJ /F4 1 Tf 2.3104 0 TD [([8)19.6(])-321(showed)-317.4(a)-319.8(marked)-323.1(effect)-313(on)-314.5(brady-)]TJ -7.5115 -1.0641 TD [(kini)-7.8(n-indu)-8.6(ced)-247.8(b)-6.5(ronchoc)-7.7(onstriction)-260.1(in)-254.3(mild)-255.7(asthmatic)-258.6(sub-)]TJ T* [(ject)-8.6(s)-610.8(was)-611(chosen.)-615.8(The)-610(nebuli)-9.7(zer)-607.9(charact)-10.9(eristics)-621.2(were)]TJ T* [(compa)-7.8(rable)-270.4(to)-260(those)-269.6(used)-260.7(by)-263.3(the)-266.8(latter)-258.8(group)-261.5(apart)-270.4(from)-265.5(a)]TJ T* [(higher)-304.9(output)-299.6(by)-291.7(the)-295.3(curren)-8.6(t)-293.4(nebuli)-9.7(zer)46.5(.)-290.6(K)]TJ 6.974 0 0 6.974 473.272 410.23 Tm 0.0001 Tc (HARITONOV)Tj /F5 1 Tf 9.963 0 0 9.963 516.302 410.23 Tm 0 Tc [(et)-294.5(al.)]TJ /F4 1 Tf -20.7762 -1.0641 TD [([9])-369.7(showed)-368.6(that)-366.7(1)-365(m)0(g)]TJ 6.974 0 0 6.974 401.612 399.628 Tm (L)Tj 9.963 0 0 9.963 405.864 399.628 Tm [(-NMMA)-370(signifi)-9.6(cantly)-368.7(decreas)-9.8(ed)]TJ -9.691 -1.0641 TD [(the)-283.9(peak)-282.7(exhale)-8.2(d)-279.6(N)0(O)-282.5(i)0(n)-277.1(healt)-9.4(hy)-274.7(c)-6.9(ontrol)-284.1(subjects)-287.2(for)]TJ /F9 1 Tf 20.964 0 TD ($)Tj /F4 1 Tf 0.8365 0 TD (30)Tj -21.8005 -1.0641 TD [(min)-7.8(.)-336.1(The)-336.9(curren)-8.6(t)-333.2(data)-342(confi)-8.2(rm)-336.3(these)-338.2(findi)-10.2(ngs)-333.5(as)-338.9(exhale)-8.2(d)]TJ T* [(NO)-532.9(level)-9.4(s)-525.5(after)-533.7(inhal)-9(ation)-532.5(of)-532.3(2)-524.3(m)0(g)]TJ 6.974 0 0 6.974 466.753 367.824 Tm (L)Tj 9.963 0 0 9.963 470.948 367.824 Tm [(-NM)-9.8(MA)-530.9(led)-528.6(to)]TJ -16.2238 -1.0641 TD [(signi)-9.8(ficant)-313.3(inhibit)-9.2(ion)-306.3(o)-6.5(f)-304(exhale)-8.2(d)-308.1(N)0(O)-311(level)-9.4(s)-303.6(for)]TJ /F9 1 Tf 18.9951 0 TD ($)Tj /F4 1 Tf 0.8365 0 TD 0.3083 Tc [(1h)308.3(.A)308.3(s)]TJ -19.8316 -1.0641 TD 0 Tc [(all)-263.5(of)-259.2(the)-266.8(first)-263.3(MBS)-264.2(challenges)-265.6(wer)-8.2(e)-257.2(compl)-9.7(eted)-262.3(withi)-9.2(n)-256.8(3)0(0)]TJ T* [(min)-218.4(and)-218.9(the)-215.6(second)-217.1(chall)-9.4(enges)-216.4(proceed)-8.2(ed)-212.5(wi)-7.8(thin)-212.7(1)-6.5(0.5\2132.3)]TJ 0 -1.0698 TD [(min)-275.3(after)-272(the)-272.5(first)-274.7(challenge,)-275.4(it)-273.8(was)-269.6(like)-8.2(ly)-265.7(that)-275.7(the)-266.8(dose)-272.1(of)]TJ 6.974 0 0 6.974 309.316 314.759 Tm (L)Tj 9.963 0 0 9.963 313.568 314.759 Tm [(-NMMA)-478.1(chosen)-473.2(was)-474.4(pharmacolo)-10.3(gical)-9.4(ly)-470.5(active)-471.5(in)-470.5(the)]TJ ET 1 i 58.28 768.302 478.205 -0.51 re f 222.633 753.335 112.876 -0.283 re f 364.082 753.335 112.819 -0.283 re f 58.28 727.427 478.205 -0.454 re f 58.28 673.171 478.205 -0.51 re f BT /F3 1 Tf 8.966 0 0 8.966 58.28 772.667 Tm [(Table)-331.9(1.)-336.7(\261)-333.2(Effect)-334.8(of)]TJ /F12 1 Tf 8.9343 0 TD (N)Tj /F3 1 Tf 6.725 0 0 5.977 144.85 776.636 Tm (G)Tj 8.966 0 0 8.966 150.123 772.667 Tm (-mono-methyl-)Tj 6.276 0 0 6.276 207.723 772.667 Tm (L)Tj 8.966 0 0 8.966 211.181 772.667 Tm [(-arginine)-336.3(on)-331.3(refractorines)-334.8(to)-330.4(sodium)-333.7(metabisulphite)-339.6(\(MBS\))]TJ /F4 1 Tf 4.9319 -1.7135 TD [(1st)-330.8(challenge)-10324.6(2nd)-333.6(challenge)]TJ -13.1706 -1.6629 TD [(Baseline)-334.7(FEV)]TJ 7.173 0 0 7.173 187.654 742.393 Tm (1)Tj 8.966 0 0 8.966 161.575 732.926 Tm (L)Tj 7.1259 1.0559 TD [(Max.)-336.9(fall)-332.3(in)]TJ 0.8599 -1.0559 TD (FEV)Tj 7.173 0 0 7.173 249.959 732.926 Tm (1)Tj 8.966 0 0 8.966 253.531 732.926 Tm (%)Tj 6.1143 1.0559 TD (AUC)Tj -0.4679 -1.0559 TD (L)Tj /F10 1 Tf 0.6007 0.2213 TD (.)Tj /F4 1 Tf 0.2719 -0.2213 TD (min)Tj 6.725 0 0 5.977 325.814 736.894 Tm (-1)Tj 8.966 0 0 8.966 366.916 742.393 Tm [(Max.)-330.6(fall)-338.6(in)]TJ 0.8536 -1.0559 TD (FEV)Tj 7.173 0 0 7.173 391.408 732.926 Tm (1)Tj 8.966 0 0 8.966 394.979 732.926 Tm (%)Tj 6.1079 1.0559 TD (AUC)Tj -0.4616 -1.0559 TD (L)Tj /F10 1 Tf 0.6007 0.2213 TD (.)Tj /F4 1 Tf 0.2719 -0.2213 TD (min)Tj 6.725 0 0 5.977 467.263 736.894 Tm (-1)Tj 8.966 0 0 8.966 516.586 742.393 Tm (RI)Tj 0.0822 -1.0559 TD (%)Tj -51.1966 -1.998 TD [(Assessment)-6272.8(3.32)-7854.4(26)-6903.6(1)32.1(1)-6904.1(16)-7137.6(6)-6145.4(5)0(5)]TJ 0 -1.0559 TD [(Placebo)-7811.8(3.33)-7854.4(26)-6903.6(1)32.1(1)-6904.1(15)-7137.6(5)-6145.4(4)0(9)]TJ 6.276 0 0 6.276 58.28 696.075 Tm (L)Tj 8.966 0 0 8.966 62.079 696.075 Tm [(-NMMA)-6993.2(3.24)-7854.4(27)-6891(10)-6884.6(15)-7137.6(5)-6145.4(5)0(0)]TJ -0.4236 -1.0559 TD [(95%)-334.1(CI)-6763.9(-0.05\2610.2)-5662.2(-4.7\2612.3)-4562.5(-1.2\2612.1)-4315.9(-6.16\2614.6)-4315.4(-1.7\2611.7)-3822.8(-20\26118)]TJ T* [(p-value)-8231.8(0.2)-7728.5(0.42)-6140.9(0.57)-6381.2(0.7)-6641(1.0)-5641.9(0.9)]TJ 0 -1.9475 TD [(Maximum)-237(fall)-237.4(in)-235.3(forced)-238.7(expiratory)-241.4(volume)-234.9(in)-235.3(one)-238.5(second)-231.6(\(FEV)]TJ 7.173 0 0 7.173 282.898 659.679 Tm (1)Tj 8.966 0 0 8.966 286.469 659.679 Tm [(\),)-237.3(area)-238.5(under)-232.1(the)-240.9(percentage)-237.4(change)-236.5(in)-235.3(FEV)]TJ 7.173 0 0 7.173 439.427 659.679 Tm (1)Tj 8.966 0 0 8.966 445.153 659.679 Tm [(curve)-231.9(\(AUC\))-238.3(over)-239(20)-232.9(min)]TJ -43.1475 -1.0559 TD [(for)-291.3(the)-285.2(first)-289.9(and)-282.8(the)-291.5(second)-288.5(MBS)-287(challenge)-290.1(and)-282.8(refractory)-291.3(index)-290.5(\(RI\).)-286.7(V)104.7(alues)-291.4(are)-289.9(presented)-283.8(as)-290.8(mean,)-286.8(standard)-290.9(errors)-285.3(are)-289.8(given)-290.5(in)-285.9(text.)]TJ T* [(95%)-334.1(CI:)-335.3(95%)-334.1(confidence)-332.5(interval)-338.7(of)-335.1(the)-335.8(diff)10.4(erence)-332.1(between)-336.5(placebo)-333.3(and)]TJ 6.276 0 0 6.276 325.02 640.743 Tm (L)Tj 8.966 0 0 8.966 328.819 640.743 Tm (-NMMA.)Tj ET 0 0 0 1 K 0 J 0 j 0.5 w 3.864 M []0 d /GS3 gs 121.753 426.466 m 128.753 379.216 l 142.127 345.341 l 155.627 356.591 l 168.877 367.591 l 188.627 378.841 l 222.252 387.466 l 255.502 395.966 l S [2 2 ]0 d 255.502 394.716 m 222.252 392.716 l 188.752 377.216 l 168.877 365.966 l 155.502 352.217 l 142.127 343.217 l 128.878 376.591 l 121.753 426.091 l S 3.864 M []0 d 92.128 329.967 m 92.128 458.591 l 92.003 425.966 m 88.628 425.966 l 92.128 458.341 m 88.628 458.341 l 92.128 393.716 m 88.628 393.716 l 92.003 361.717 m 88.628 361.717 l 92.128 330.217 m 88.628 330.217 l 92.174 330.285 m 282.673 330.285 l 255.673 330.285 m 255.673 327.66 l 222.048 330.285 m 222.048 327.66 l 188.299 330.285 m 188.299 327.66 l 155.049 330.285 m 155.049 327.66 l 121.549 330.285 m 121.549 327.66 l S BT /F17 1 Tf 10 0 0 10 72.503 326.308 Tm 0 0 0 1 k /GS4 gs ( -30)Tj 0 3.1545 TD ( -20)Tj 0.25 3.2079 TD (-10)Tj 0.7 3.2035 TD (0)Tj -0.45 3.2648 TD (10)Tj 0 10 -10 0 70.128 366.341 Tm (Fall in FEV)Tj 0 8 -8 0 70.128 406.441 Tm (1)Tj 0 10 -10 0 70.128 410.089 Tm ( %)Tj 10 0 0 10 63.378 454.466 Tm (a\))Tj ET 3.864 M [2 2 ]0 d /GS3 gs 256.127 276.967 m 222.877 260.967 l 189.127 251.592 l 169.002 243.592 l 155.752 234.842 l 142.502 231.592 l 129.128 241.342 l 122.628 276.717 l S 3.864 M []0 d 122.503 276.717 m 129.128 244.342 l 142.502 229.842 l 155.877 239.217 l 169.127 247.467 l 189.127 251.092 l 223.127 259.217 l 256.377 274.717 l S 3.864 M 140.774 230.138 m 140.774 231.105 141.558 231.888 142.524 231.888 c 143.491 231.888 144.274 231.105 144.274 230.138 c 144.274 229.172 143.491 228.388 142.524 228.388 c 141.558 228.388 140.774 229.172 140.774 230.138 c b 3.864 M 129.128 235.342 m 129.128 249.967 l S 3.864 M 127.354 244.004 m 127.354 244.97 128.138 245.754 129.104 245.754 c 130.071 245.754 130.854 244.97 130.854 244.004 c 130.854 243.037 130.071 242.254 129.104 242.254 c 128.138 242.254 127.354 243.037 127.354 244.004 c b 0 0 0 0 k 120.492 276.842 m 120.492 277.971 121.375 278.887 122.463 278.887 c 123.552 278.887 124.434 277.971 124.434 276.842 c 124.434 275.712 123.552 274.797 122.463 274.797 c 121.375 274.797 120.492 275.712 120.492 276.842 c b 120.735 278.682 3.518 -3.84 re B 3.864 M 92.114 181.387 m 92.114 310.011 l 91.989 277.387 m 88.614 277.387 l 92.114 309.761 m 88.614 309.761 l 92.114 245.137 m 88.614 245.137 l 91.989 213.137 m 88.614 213.137 l 92.114 181.637 m 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