Interactions between noradrenaline and alpha 2-adrenoceptor agonists in the superior mesenteric arterial bed of the rat.
Interactions between alpha 2-agonists and noradrenaline vasoconstrictor responses were studied in the superior mesenteric arterial bed of the rat by use of perfusion both in situ with blood and in vitro with Krebs-Henseleit solution. Xylazine (1.9 X 10(-6) mol) administered into the perfusion circuit reduced the maximum response to noradrenaline in the in situ preparation by 35% and decreased the pD50 for noradrenaline from 8.5 +/- 0.01 to 7.9 +/- 0.13 (n = 7). Yohimbine (1 mg kg-1, i.v.) gave a small parallel shift in the noradrenaline log dose-response curve and prevented the reduction in the maximum response by subsequent administration of xylazine. In vitro, xylazine (1.9 X 10(-6) mol) also gave a long-lasting reduction of 37% in the maximum response but did not affect the mid-point sensitivity to noradrenaline. Yohimbine (10(-6) M) did not change either of these effects. Clonidine (1.9 X 10(-6) mol) did not affect the maximum response to noradrenaline in vitro but did reduce the pD50 from 7.72 +/- 0.17 to 6.9 +/- 0.17 (n = 6). Yohimbine did not change these effects. Guanfacine (1.8 X 10(-6) mol) had no effect on the sensitivity of the in vitro preparation to noradrenaline but did reduce the maximum response by 20%. Yohimbine (10(-6)M) prevented the depression of the maximum response. It is concluded xylazine and clonidine interfere with noradrenaline induced vasoconstriction only to a limited extent through their interaction with alpha 2-adrenoceptors and that some other, as yet uncharacterized mechanism which may be activated by their aryl amidine structure, is responsible for their in vitro effects.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014991:Xylazine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014991:Xylazine; D009638:Norepinephrine