RT Journal Article
SR Electronic
T1 Endogenous Nitric Oxide Modulates Acetylcholine-induced Edema and Vasoconstriction in Isolated Perfused Rabbit Lungs
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 589
OP 597
VO 274
IS 2
A1 A. DELAUNOIS
A1 P. GUSTIN
A1 M. ANSAY
YR 1995
UL http://jpet.aspetjournals.org/content/274/2/589.abstract
AB The modulatory role of endogenous nitric oxide (NO) on pulmonary edema induced by acetylcholine (ACh), capsaicin, substance P (SP) and 5-hydroxytryptamine (5-HT) was investigated by using an inhibitor of NO synthase, N-ω-nitro-l-arginine (L-NNA). The effects of endogenous NO on the hemodynamic response to ACh, 5-HT and SP were also investigated. The capillary filtration coefficient (Kf,c), the total pressure gradient (▵Pt) and its four components [arterial (▵Pa), pre- (▵Pá) and post-capillary (▵Pv), and venous gradient (▵Pv)] were evaluated on isolated, ventilated, perfused rabbit lungs. ACh (10-8 to 10-4 M) and SP (10-10 to 10-6 M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10-4 M) and 5-HT (10-4 M) also increased this parameter. L-NNA (10-4 M) completely inhibited the effects of ACh and capsaicin on the Kf,c, without preventing the effects of SP and 5-HT. ACh induced a concentration-dependent vasoconstriction in the precapillary segment. Pretreatment with L-NNA enhanced this increase in ▵Pá but also increased ▵Pv and ▵Pv. 5-HT increased ▵Pt and ▵Pa proportionally to the concentration. This effect was enhanced by L-NNA, which also increased ▵Pá. SP had no significant hemodynamic effect. Pretreatment with L-NNA did not modify the response to SP. Sodium nitroprusside (10-5 M) induced a left shift of the concentration-response curve to ACh on the Kf,c, although it did not change the response to SP. Sodium nitroprusside also inhibited the hemodynamic effect of ACh. It was concluded that endogenous NO is involved in ACh- and capsaicin-induced edema via a prejunctional stimulatory effect on the C-fibers. Endogenous NO can also modulate ACh- and 5-HT-induced vasoconstriction by exerting a vasodilator action on the whole pulmonary vascular bed. 1995 by The American Society for Pharmacology and Experimental Therapeutics