L-arginine analogues blunt prostaglandin-related dilation of arterioles.
The effects of arginine analogues, inhibitors of endothelium-derived nitric oxide synthesis, on dilation of arterioles in response to various vasoactive substances were studied. At 65 mmHg intravascular pressure, isolated arterioles of rat cremaster muscle developed tone spontaneously and achieved control diameters similar to those observed in vivo (84.1 +/- 2.0 microns vs. passive diameter: 161.3 +/- 3.4 microns). Acetylcholine (ACh, 5 x 10(-8) M), sodium nitroprusside (SNP, 5 x 10(-8) M), arachidonic acid (AA, 10(-7) M), prostaglandin E2 (PGE2, 10(-9) M), and adenosine (ADO, 10(-6) M) were added to the Krebs bicarbonate buffer solution, suffusing the vessels. The peak vasodilator effects of all agents were studied before and after the administration of various doses of N omega-nitro-L-arginine (L-NNA; 10(-5), 10(-4), and 10(-3) M), which significantly reduced, in a dose-dependent manner, the basal diameter of arterioles by 3.6, 15.2, and 18.9%, respectively. The lowest concentration of L-NNA significantly inhibited arteriolar dilations to ACh by approximately 26%. Higher concentrations of L-NNA and N omega-monomethyl-L-arginine (L-NMMA; 10(-4) M) caused a further significant reduction in the dilation to ACh (to approximately 47%) and also significantly reduced dilator responses to AA and PGE2. In the presence of the highest concentration of L-NNA (10(-3) M), dilation to SNP and ADO were also significantly reduced. Removal of endothelium abolished dilation to ACh and AA but did not alter that to SNP, PGE2, or ADO.(ABSTRACT TRUNCATED AT 250 WORDS)
Koller
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A
Department of Physiology, New York Medical College, Valhalla 10595.
Sun
D
D
Messina
E J
EJ
Kaley
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G
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D001095:Arachidonic Acids; D011453:Prostaglandins; D009599:Nitroprusside; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000241:Adenosine; D015232:Dinoprostone; D000109:Acetylcholine