Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin.
Inhibitors of nitric oxide (NO) synthesis increase blood pressure and decrease regional blood flow. We investigated whether blockade of the renin-angiotensin, sympathetic nervous, prostaglandin or vasopressin systems attenuates the effects of the NO synthesis inhibitor NG-nitro-L-arginine (L-NOARG) on mean arterial pressure and renal blood flow in anesthetized male Sprague-Dawley rats. Treatment with L-NOARG (10 mg kg-1, i.v. bolus plus infusion at 20 mg kg-1 hr-1) increased mean arterial pressure from 113 +/- 2 to 133 +/- 4 mm Hg, decreased renal blood flow from 7.7 +/- 0.6 to 4.3 +/- 0.6 ml min-1 g-1 and increased renal vascular resistance from 15.8 +/- 1.8 to 36.9 +/- 6.1 mm Hg/ml min-1 g-1. These effects were attenuated in rats pretreated with L-arginine to interfere with the inhibitory action of L-NOARG on NO synthesis, but not in rats pretreated with D-arginine. Acetylcholine did not relax aortic rings taken from rats treated with L-NOARG, consistent with inhibition of NO-mediated vasorelaxation. The pressor and renal vasoconstrictor effects of L-NOARG were not impaired in rats separately pretreated with either chlorisondamine, captopril, prazosin, indomethacin or d(CH2)5Tyr(Me)AVP, or in rats pretreated with chlorisondamine, captopril and indomethacin in combination. Collectively, these data argue against significant contribution of the sympathetic nervous system, the renin-angiotensin system, vasopressor prostanoids or vasopressin to the mechanisms of L-NOARG-induced elevation of mean arterial pressure and renal vasoconstriction in anesthetized rats.
Pucci
M L
ML
Department of Pharmacology, New York Medical College, Valhalla.
Lin
L
L
Nasjletti
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000031:analogs & derivatives*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D011311:Pressoreceptors / Q000187:drug effects*; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology*
D011453:Prostaglandins; D014667:Vasopressins; D000804:Angiotensin II; D001127:Arginine Vasopressin; D019335:Nitroarginine; D009569:Nitric Oxide; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D001120:Arginine