Regional and cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats.
1. Regional haemodynamic responses to i.v. bolus doses (0.1-10.0 mg kg-1) of NG-nitro-L-arginine methyl ester (L-NAME) were measured in conscious, Long Evans rats (n = 8) chronically instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and intravascular catheters. 2. L-NAME caused dose-dependent pressor effects associated with renal, mesenteric and hindquarters vasoconstrictions. The mesenteric vascular bed showed earlier onset with more rapid, and greater, maximum vasoconstrictions than the renal or hindquarters vascular beds; however, the hindquarters vasoconstriction was more persistent. D-NAME was without significant effects (n = 2). 3. Primed infusion of L-arginine (100 mg kg-1 bolus followed by 100 mg kg-1 h-1 infusion), starting 10 min after an i.v. bolus injection of L-NAME (10 mg kg-1), caused significant reversal of the pressor responses, and renal and mesenteric vasoconstrictions, but not of the hindquarters vasoconstriction. Primed infusions of L-arginine (100 mg kg-1, 100 mg kg-1 h-1) starting 5 min after L-NAME (1 mg kg-1) additionally caused some reversal of the hindquarters vasoconstriction, but this effect was transient. 4. Primed infusion of L-arginine (100 mg kg-1, 100 mg kg-1 h-1) starting 30 min before i.v. bolus injection of L-NAME (10 mg kg-1) caused significant attenuation of the pressor effects and the renal and mesenteric vasoconstrictions but not of the hindquarters vasoconstriction. 5. In a separate group of rats (n = 8) chronically instrumented with thoracic aortic electromagnetic flow probes for the measurement of cardiac haemodynamics, i.v. bolus injection of L-NAME (10mgkg-1) produced significant reductions in total peripheral conductance, cardiac output, stroke volume, peak thoracic aortic flow and the maximum rate of rise of aortic flow; these were coincident with the maximum pressor and vasoconstrictor effects. 6. These results, collectively, are consistent with L-NAME interfering with L-arginine-nitric oxide pathways that have important influences on regional vascular conductances in vivo. The pressor effect resulting from L-NAME-induced vasoconstrictions is offset by a substantial reduction in cardiac function that may depend on direct and/or indirect effects of L-NAME on the heart.
Gardiner
S M
SM
Department of Physiology & Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
Compton
A M
AM
Kemp
P A
PA
Bennett
T
T
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester