Neural mechanism of pressor action of nitric oxide synthase inhibitor in anesthetized monkeys.
Intravenous injection of NG-nitro-L-arginine (L-NA), a nitric oxide synthase inhibitor, elevated mean blood pressure by 29.0 +/- 4.9 mm Hg and decreased heart rate by 40.7 +/- 5.6 beats per minute in anesthetized Japanese monkeys (n = 6), whereas NG-nitro-D-arginine was without effect. After pretreatment with pentolinium, the magnitude of the pressure elevation by L-NA was significantly less than that after pretreatment with phentol-amine. The reduced blood pressure by either of the pretreatment drugs was compensated to control levels by a continuous infusion of angiotensin II before L-NA administration. Isolated monkey distal mesenteric arteries (150 to 200 microns OD) without endothelium responded to nerve stimulation by nicotine with a contraction, which was abolished by prazosin alone or in combination with alpha, beta-methylene ATP. In the strips thus treated and contracted with prostaglandin F2 alpha, nicotine caused a relaxation that L-NA abolished. L-NA but not NG-nitro-D-arginine reversed the inhibition. Histochemical staining of NADPH diaphorase, considered to be identical to nitric oxide synthase in neuronal tissues, demonstrated that positively stained nerve fibers were consistently present in the adventitia of monkey distal mesenteric arteries and arterioles. These results strongly suggest that nitroxidergic vasodilator nerves innervate peripheral small arteries and arterioles in the monkey and that these nerves participate in the regulation of systemic blood pressure. High blood pressure caused by nitric oxide synthase inhibitors is associated with an elimination of nitroxidergic nerve function together with an impairment of the basal release of nitric oxide from the endothelium.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Science, Japan. okamura@bellebsd.shiga-med.ac.jp
Ayajiki
K
K
Toda
N
N
D000818:Animals; D001158:Arteries / Q000294:innervation; D001794:Blood Pressure / Q000187:drug effects*; D005260:Female; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008251:Macaca; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009412:Nerve Fibers / Q000201:enzymology; D009424:Nervous System Physiological Phenomena; D009538:Nicotine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014661:Vasoconstriction
D019335:Nitroarginine; D009538:Nicotine; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase