Nonendothelial aortic source of nitric oxide in Wistar-Kyoto normotensive and spontaneous hypertensive rats.
Using a recognized inhibitor of nitric oxide (NO) synthesis, Nw-nitro L-arginine methyl ester (L-NAME), we tested the hypothesis of the existence of a nonendothelial source of NO in vascular tissue using rings of rat thoracic aorta in which endothelial cells have been removed by mechanical abrasion and have totally lost their endothelium-dependent relaxation. Contractility of the muscle was tested by recording the concentration-dependent contraction of the preparations induced by an alpha-adrenergic agonist, phenylephrine. Contractility in aortas from Wistar-Kyoto normotensive rats (WKY) and spontaneous hypertensive rats (SHR) was not significantly affected by a 30-min to 2-hour incubation with L-NAME prior to agonist stimulation. However, preparations incubated for 30 min with 1 mM L-arginine (L-ARG) and then washed for 1 h in standard Krebs solution had a significantly reduced contraction to phenylephrine in both WKY and SHR. In these preparations pretreated with L-ARG, L-NAME significantly increased contractility in both WKY and SHR; this effect was prevented by L-ARG but not by D-arginine. Responses to phenylephrine were not inhibited by L-ARG when preparations were incubated from the beginning of the experiment with 1 mM cycloheximide, thus suggesting a dependence on protein synthesis of the attenuation of contraction seen with L-ARG. Intact aortic rings processed for NADPH diaphorase histochemistry, a putative marker for NO synthase, showed NADPH diaphorase reactivity only in the endothelial layer and in the adventitia.(ABSTRACT TRUNCATED AT 250 WORDS)
Bourreau
J P
JP
Department of Biomedical Sciences, McMaster University, Hamilton, Canada.
Kitchener
P
P
Kwan
C Y
CY
Daniel
E E
EE
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D009252:NADPH Dehydrogenase; D019331:NG-Nitroarginine Methyl Ester