Regulation of arteriolar tone and responses via L-arginine pathway in skeletal muscle.
With in vivo television microscopy, changes in arteriolar diameter to topical administration of various vasoactive agents were examined in the absence or in the presence of NG-monomethyl-L-arginine (L-NMMA, topical 100 microM) or NG-nitro-L-arginine (L-NNA, 2.5 microM, 20 microliters/min ia), specific inhibitors of endothelium-derived relaxing factor (EDRF) biosynthesis. In cremaster muscle arterioles (15-22 microns) of rats (n = 6-11), dilations to acetylcholine (1-100 ng) were significantly inhibited (60-70%) by either of the arginine analogues. This inhibition was reversed by subsequent administration of 1 mM L-arginine. Dose-dependent constriction to norepinephrine was enhanced by L-NMMA. Indomethacin treatment reduced arteriolar dilation to bradykinin (BK, 1-100 ng), which was significantly inhibited by additional administration of L-NNA. Application of L-NNA first, followed by additional indomethacin, elicited similar results. Dilations to sodium nitroprusside and adenosine were not reduced in the presence of the inhibitors. L-NMMA or L-NNA caused no change in systemic blood pressure but elicited a significant reduction in arteriolar diameter; this effect was not reversed by 1 mM L-arginine. These data demonstrate the presence of an L-arginine pathway to produce EDRF (nitric oxide) in skeletal muscle microcirculation that mediates and/or modulates arteriolar responses to vasoactive agents and could contribute to the regulation of basal vascular tone.
Kaley
G
G
Department of Physiology, New York Medical College, Valhalla 10595.
Koller
A
A
Rodenburg
J M
JM
Messina
E J
EJ
Wolin
M S
MS
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009132:Muscles / Q000098:blood supply*; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains; D014666:Vasomotor System / Q000502:physiology*; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D001120:Arginine; D001920:Bradykinin; D007213:Indomethacin