Effects of Prazosin and Phentolamine on Cardiac Presynaptic α-Adrenoceptors in the Cat, Dog and Rat

Abstract

In cats, dogs and rats, clonidine (20.0 μg/Kg, i.v.) reduced the sustained tachycardia evoked by a continuous electrical stimulation of cardiac sympathetic nerve fibres. This effect of clonidine resulting from stimulation of cardiac presynaptic α-adrenoceptors could be completely antagonized by phentolatnine and prazosin in the dog and the cat, whereas in the rat, prazosin, unlike phentolamine, failed to effectively inhibit the clonidine induced reduction in heart rate. The calculated doses of phentolamine and prazosin needed to produce a 50% antagonism were of similar magnitude in the dog, but in the cat prazosin was about three times less potent than phentolamine. As opposed to clonidine, LD 3098, a potent vascular postsynaptic α-adrenoceptor stimulating imidazoline, and phenylephrine (20.0 μg/Kg, i.v.) did not significantly alter the sympathetic tachycardia in the pithed rat and the spinal dog. These results indicate that compounds stimulating postsynaptic α-adrenoceptors may be inactive as agonists of cardiac presynaptic α-adrenoceptors within the same animal species. Furthermore, a compound showing selective activity as an antagonist of vascular α-adrenoceptors in one species may not necessarily exert the same selective effects in other animals as demonstrated here for prazosin.