Abstract
The role of vascular alpha 1B-adrenergic receptors in the regulation of arterial pressure (MAP) and heart rate (HR) was examined by assessing the effect of i.v. chloroethylclonidine (CEC; irreversible alpha 1B antagonist) in unanesthetized, normotensive Long-Evans rats. MAP, HR and the pressor response to i.v. phenylephrine (PE) were monitored for 24 hr after saline or CEC (15 mg/kg and 25 mg/kg) injection. Neither i.v. saline nor CEC affected MAP or HR throughout the course of the study, yet the PE response was maximally inhibited (> 75% at 15 min) by both doses of CEC. The PE response recovered by 2 hr at the 15-mg/kg dose but remained inhibited up to 4 hr at 25 mg/kg. At 24 hr, all cardiovascular parameters returned to control levels. CEC (100 microM, 30 min) produced irreversible blockade of norepinephrine-induced contractions in rat aortic rings; prazosin (10 nM) and sodium thiosulphate (1 mM, a reagent that inactivates aziridinium ions) reversed CEC's inhibitory effect. Precyclized CEC and its hydrolysis product beta-hydroxyethylclonidine (beta-HEC) poorly antagonized aortic alpha 1B-receptors. Ex vivo analysis of aortic rings from saline and CEC-treated rats showed that PE-induced contractions were shifted to the right and maximally depressed in a dose-dependent manner after 24 hr. These results suggest that 1) CEC produces long lasting blockade of alpha 1B-adrenoceptors in vitro and in vivo via formation of an aziridinium ion intermediate and 2) vascular alpha 1B-adrenoceptors are not coupled to the tonic physiological regulation of MAP in the rat.