The mechanism of the sympathoinhibitory action of urapidil: role of 5-HT1A receptors.

1. An investigation was carried out to determine if the sympathoinhibition caused by urapidil is due to activation of 5-HT1A receptors by investigating whether it could be reversed by the non-selective 5-HT1A receptor antagonist spiperone. To control for the possibility of functional antagonism by spiperone, the ability of spiperone to reverse the sympathoinhibition caused by clonidine was also investigated. These experiments were carried out in anaesthetized prazosin-pretreated cats to prevent the alpha 1-adrenoceptor antagonist action of urapidil and spiperone from masking any effects observed. 2. Cats were anaesthetized with alpha-chloralose and simultaneous recordings were made of whole cardiac, splanchnic and renal nerve activities, blood pressure, heart rate and femoral arterial flow (from which conductance was derived). All animals were initially pretreated with prazosin (1 mg kg-1, i.v.) given in divided doses (0.75 followed 10 min later by 0.25 mg kg-1), then either urapidil (0.75 mg kg-1, i.v.) or clonidine (10 micrograms kg-1, i.v. in two divided doses) followed by 3 separate injections of spiperone (1 mg kg-1, i.v.). In another set of experiments urapidil was given followed by injections of the appropriate vehicle for spiperone, while in another set urapidil was replaced with an injection of the appropriate vehicle followed by injections of spiperone. In the experiments with clonidine, the alpha 2-adrenoceptor antagonist Wy 26392 (0.3 mg kg-1) was given after the last injection of spiperone. 3. The prazosin pretreatment caused a fall in blood pressure associated with femoral vasodilatation, a small bradycardia and little change in cardiac, splanchnic or renal nerve activities.(ABSTRACT TRUNCATED AT 250 WORDS)