Study of prejunctional beta-adrenoceptors in kidneys of normotensive and hypertensive rats using the new beta-adrenoceptor blocking drug tertatolol.

Abstract

The prejunctional beta-adrenoceptors present in the isolated perfused kidney of normotensive rats (NR) and spontaneously hypertensive rats (SHR) were compared and the effects of tertatolol on these receptors were investigated. Kidneys of NR (Wistar + Wistar-Kyoto [WKY]) and SHR, were continuously perfused with Tyrode solution at constant flow and the changes in perfusion pressure were monitored. The constrictor responses to norepinephrine (2-8 X 10(-10) moles) were slightly but significantly decreased by isoproterenol (2 X 10(-7) M) to a similar degree in NR and SHR. Tertatolol (3 X 10(-7) M) did not alter the constriction caused by norepinephrine, but abolished the dilator response to isoproterenol. Electrical stimulation of renal nerves (8 Hz) evoked constrictions in both NR and SHR; these constrictor responses were augmented in the presence of isoproterenol (2 X 10(-7) M) to a similar extent in NR and SHR. In kidneys of NR and SHR, previously incubated with 3H norepinephrine, renal nerve electrical stimulation (6 Hz) evoked an overflow of the 3H transmitter. This overflow was enhanced by isoproterenol (2 X 10(-6) M) to a similar degree in NR and SHR. Both the augmented constrictor response and the augmented overflow of 3H norepinephrine caused by electrical stimulation in the presence of isoproterenol, were inhibited by tertatolol (3 X 10(-7) M). Our results show that the beta-receptor agonist isoproterenol evokes comparable effects at prejunctional beta-adrenoceptors in kidneys of NR and SHR; they also show that tertatolol is an inhibitor of pre- and postjunctional beta-adrenoceptors in the renal circulation of the rat.