Buspirone, a 5-HT_1A receptor agonist, dilates the perfused rat uterine vascular bed through α₁-adrenoceptor blockade

In the perfused rat uterine vascular bed, 5-hydroxytryptamine (5-HT) produced dose-dependent vasoconstrictor responses. Buspirone, a selective 5-HT_1A receptor agonist, was not effective at low doses but produced a response at high doses. When perfusion pressure was raised with phenylephrine, responses to 5-HT were enhanced while buspirone produced dose-dependent vasodilator responses. Buspirone did not produce vasodilation when perfusion pressure was raised with vasopressin or U46619. Buspirone-induced vasodilator responses were not affected by selective 5-HT_1A 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-phenylpropanamide (WAY 100478), indicating that specific 5-HT_1A receptors might not be involved in buspirone-induced vasodilation. Buspirone (3 × 10^-5 M) and prazosin (3 × 10^-9 M) antagonized noradrenaline-induced constriction with dose 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 ratio is closer to the sum of their individual dose ratios less 2 (i.e. DR_p+DR_b-2) than it is to the product of their individual dose ratios, our data suggest an interaction of buspirone with α₁-adrenoceptors. Buspirone also protected adrenoceptors against inactivation by phenoxybenzamine confirming that buspirone interacted with α₁-adrenoceptors. We concluded that buspirone-induced vasodilation of the perfused rat uterine vascular bed is mediated through blockade of α₁-adrenoceptors rather than through 5-HT_1A receptors.