Evidence that spiperone reverses the additional sympathoinhibitory action of urapidil in anaesthetised, prazosin-pretreated cats

Abstract

Urapidil is a novel antihypertensive agent which lowers blood pressure by decreasing total peripheral resistance and also reduces central sympathetic outflow [1–3]. As urapidil blocks α₁ -adrenoceptors, this profile of action is what would be expected from such a drug. However, many authors have been unable to relate the central sympathoinhibitory effect of urapidil to its α₁-adrenoceptor blocking action [3]. It has been suggested that urapidil could also be acting on 5-HT_1A receptors [3] and the ability of urapidil to bind to these receptors [4] supports such a hypothesis, However, using the intravertebral route of administration [5] (giving drugs via the vertebral artery) (–)pindolol, which attenuated the hypotensive action of several putative 5-HT_1A receptor agonists, did not influence the hypotensive response to urapidil. This suggests that the central hypotensive action of urapidil is not related to an agonist action at 5-HT_1A receptors but it is possible that the α₁-adrenoceptor antagonist action of urapidil is masking this inhibition, and/ or (–) pindolol may not be the ‘ideal’ antagonist. The present experiments were designed to overcome these problems by, first, pretreating the animals with a large dose of prazosin to ensure complete α ₁-adrenoceptor blockade and by using spiperone as the antagonist as spiperone has been reported to reverse the sympathoinhibitory action of 8-OH-DPAT [6].