A comparative study on the rat aorta and mesenteric arterial bed of the possible role of nitric oxide in the desensitization of the vasoconstrictor response to an alpha 1-adrenoceptor agonist.
1. In thoracic aortic strips with intact endothelium, the first and second (1 h later) dose-response curves obtained with methoxamine were almost the same. 2. Methoxamine caused a dose-dependent increase in perfusion pressure in the rat isolated mesenteric arterial bed, but the second (1 h later) dose-response curve for methoxamine showed a significant attenuation of the response in comparison with the first. 3. The attenuation shown by the second dose-response curve for methoxamine was significantly reduced, but not abolished, in mesenteric arterial beds without endothelium. Incubating endothelium-intact mesenteric arterial beds with NG-nitro-L-arginine (L-NOARG) caused a significant, but not complete, reversal of the attenuation shown in the second dose-response curve. 4. Incubating the mesenteric arterial bed with capsaicin, tetrodotoxin, indomethacin or with isotonic high k+ (60 mM) plus nicardipine did not affect the above attenuation seen in the second dose-response curve. 5. The guanosine 3':5'-cyclic monophosphate (cyclic GMP) level in the effluent from the perfused mesenteric arterial bed was significantly increased after the second exposure to methoxamine. This effect was significantly smaller after removal of the endothelium or pretreatment with L-NOARG. 6. These results suggest that a desensitization to methoxamine develops rapidly in the mesenteric arterial bed, but not in the aorta, and that release of nitric oxide from the endothelium plays a major role in this desensitization.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Makino
A
A
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008729:Methoxamine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D006152:Cyclic GMP; D008729:Methoxamine