Vasodilator effect of 8‐OH‐DPAT in the isolated perfused mesenteric bed of the rat: no evidence for involvement of 5‐HT1A receptors

Abstract
1. In the isolated perfused mesenteric bed of the rat, bolus administration or infusion of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT; bolus 0.3-90 nmoles, infusion 0.03-30 microM) caused dose-related decreases in phenylephrine-induced tone. 2. These vasodilator responses were not modified by the 5-HT1A receptor antagonists BMY7378 (0.3 microM) or cyanopindolol (0.1 microM). 3. A number of compounds, having a range of affinities for 5-HT1A receptors, were tested in the mesentery and also for antagonist activity at alpha 1-adrenoceptors in the rabbit isolated aorta. 4. The potency of 8-OH-DPAT, flesinoxan, ipsapirone, sumatriptan and phentolamine, at decreasing phenylephrine-induced tone in the mesentery correlated closely with antagonist potency at alpha 1-adrenoceptors (r = 0.99) but not with affinity at 5-HT1A binding sites (r = -0.2). 5. It is concluded that the vasodilator effect of 8-OH-DPAT in the mesenteric bed of the rat most probably reflects alpha 1-adrenoceptor antagonist activity.