Effects of chronic nitric oxide synthase inhibition on endothelium-dependent and -independent relaxation in arteries that perfuse skeletal muscle of swine.
The purpose of this investigation was to test the hypothesis that chronic N(G)-nitro-l-arginine methyl ester (l-NAME) treatment produces differential effects on conduit artery and resistance arteriole relaxation responses to endothelium-dependent and -independent vasodilators in arteries that perfuse skeletal muscle of swine. To test this hypothesis, conduit skeletal muscle arteries and second-order skeletal muscle (2A) arterioles were harvested from 14 Yucatan swine that were chronically administered l-NAME and from 16 controls. In vitro assessments of vasorelaxation to increasing doses of acetylcholine (ACH), bradykinin (BK), and sodium nitroprusside (SNP) were performed in both conduit and 2A arterioles. l-NAME treatment produced a significant reduction in both BK and ACH relaxation responses in the conduit arteries. In contrast, the relaxation response and/or sensitivity to SNP were significantly greater in the intact, but not denuded, conduit arterial rings from chronically l-NAME-treated swine. There were no significant effects of chronic l-NAME treatment on vasodilation of skeletal muscle arterioles. These findings suggest (1) that unlike arterioles, skeletal muscle conduit arteries do not functionally compensate for a lack of NO through the upregulation of alternative vasodilator pathways; (2) that the greater relaxation response in conduit arteries of chronically l-NAME-treated swine to SNP can be explained by alterations to the endothelium.
Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, USA.
S C
SC
Newcomer
J C
JC
Taylor
R M
RM
McAllister
M H
MH
Laughlin
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000201:enzymology; D001160:Arterioles / Q000187:drug effects* / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000201:enzymology; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000201:enzymology; D005552:Forelimb / Q000098:blood supply; D015971:Gene Expression Regulation, Enzymologic; D006614:Hindlimb / Q000098:blood supply; D020128:Inhibitory Concentration 50; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D012039:Regional Blood Flow; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester