Amplification of alpha adrenergic vasoconstriction in canine isolated mesenteric artery and vein

Abstract

The interactions between UK-14304 and other vasoconstrictor agents were investigated using isolated canine mesenteric vascular rings mounted in tissue baths for the measurement of isometric contraction. In the mesenteric artery, exposure to UK-14304 caused a small contraction, producing 8% of the KCl maximal response. In the presence of either 20 mM KCl or 10-9 M endothelin-1, which had small contractile effects, UK-14304 produced a biphasic concentration-response curve; 10-7 M rauwolscine inhibited the responses to low concentrations of UK-14304 and 10-7 M prazosin blocked the responses to high concentrations of UK-14304. In the presence of 10-8 M Bay K 8644, UK-14304 elicited a monophasic concentration-dependent contraction that was antagonized by 10-7 M prazosin, not by 10-7 M rauwolscine. In the mesenteric vein, UK-14304 elicited concentration-dependent contractions, producing 63% of the KCl maximal response. The lower part of the biphasic concentration-response curve was inhibited by 10-7 M rauwolscine and the upper part of the curve was antagonized by 10-7 M prazosin. The presence in the medium of 20 mM KCl, 10-11 M endothelin-1 or 10-9 M Bay K 8644, which increased resting tension less than 10% of the KCl maximal response, markedly enhanced the responses to UK-14304 primarily at concentrations lower than 10-6 M. The enhancement of responses were prazosin (10-7 M)- resistant and rauwolscine (10-7 M)-sensitive. In canine mesenteric artery, our data suggest that addition of threshold concentrations of either KCl or endothelin-1 enhanced UK-14304 response via amplification of both postjunctional alpha1 and alpha2 adrenoceptor-mediated responses, while the potentiating effect of Bay K 8644 may only result from amplification of postjunctional alpha1 adrenoceptor-mediated responses. In canine mesenteric vein, either KCl, endothelin-1 or Bay K 8644 enhanced the contractile response to UK-14304 through amplification of postjunctional alpha2 adrenoceptor-mediated responses.