Comparative effects of L-NNA and alkyl esters of L-NNA on pulmonary vasodilator responses to ACh, BK, and SP.
The comparative effects of the nitric oxide (NO) synthase inhibitors N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME), and N omega-nitro-L-arginine benzyl ester (L-NABE) on baseline tone and on vasodilator responses to acetylcholine (ACh), bradykinin (BK), and substance P (SP) were compared in the pulmonary vascular bed of the cat under constant flow conditions. After administration of the NO synthase inhibitors in intravenous doses of 100 mg/kg, the increase in lobar arterial pressure and the attenuation of vasodilator responses to ACh, BK, and SP were similar, whereas responses to adenosine and felodipine, endothelium-independent vasodilator agents, were not altered. In addition to inhibiting responses to ACh, BK, and substance P, the NO synthase inhibitors enhanced vasodilator responses to S-nitroso-N-acetylpenicillamine and NO. Moreover, atropine inhibited pulmonary vasodilator responses to ACh but not to SP or BK, and L-NAME or L-NABE had no effect on the decrease in heart rate in response to efferent vagal stimulation, a muscarinic receptor-mediated response that is independent of NO release. The similar inhibitory effects of L-NNA, L-NAME, and L-NABE on vasodilator responses to ACh, BK, and SP suggest that the L-arginine analogue, L-NNA, as well as the methyl and benzyl esters of L-NNA are useful probes for studying NO-mediated endothelium-dependent responses in the pulmonary vascular bed of the intact-chest cat.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheng
D Y
DY
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
DeWitt
B J
BJ
McMahon
T J
TJ
Kadowitz
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D011652:Pulmonary Circulation / Q000187:drug effects*; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D019335:Nitroarginine; D013373:Substance P; C071057:N(w)-nitroarginine benzyl ester; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester