Buspirone, a 5-HT1A receptor agonist, dilates the perfused rat uterine vascular bed through alpha(1)-adrenoceptor blockade

In the perfused rat uterine vascular bed. 5-hydroxytryptamine (5-HT) produc ed dose-dependent vasoconstrictor responses. Buspirone, a selective 5-HT1A receptor agonist, was not effective at low doses but produced a response at high doses. When perfusion pressure was raised with phenylephrine, respons es to 5-HT were enhanced while buspirone produced dose-dependent vasodilato r responses. Buspirone did not produce vasodilation when perfusion pressure was raised with vasopressin or U46619. Buspirone-induced vasodilator respo nses were not affected by selective 5-HT1A receptor antagonists, 8-[2-[4-(2 -methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]-decane-7,9-dione (BMY 7378) and N-tert-butyl-3-(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenylpropan amide (WAY 100478), indicating that specific 5-HT1A receptors might not be involved in buspirone-induced vasodilation. Buspirone (3 x 10(-5) M) and pr azosin (3 x 10(-9) M) antagonized noradrenaline-induced constriction with d ose ratios of 19.1 +/-2.9 and 11.7 +/- 2.1, respectively. The dose ratio of these antagonists in combination was 46.6 +/- 8.1. Since the combination r atio is closer to the sum of their individual dose ratios less 2 (i.e. DRp + DRb - 2) than it is to the product of their individual dose ratios, our d ata suggest an interaction of buspirone with alpha (1)-adrenoceptors. Buspi rone also protected adrenoceptors against inactivation by phenoxybenzamine confirming that buspirone interacted with al-adrenoceptors. We concluded th at buspirone-induced vasodilation of the perfused rat uterine vascular bed is mediated through blockade of alpha (1)-adrenoceptors rather than through 5-HT1A receptors. (C) 2001 Elsevier Science Inc. All rights reserved.