Study of Prejunctional Beta-Adrenoceptors in Kidneys of Normotensive and Hypertensive Rats Using the New Beta-Adrenoceptor Blocking Drug Tertatolol

Abstract

The prejunctional β-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 × 10^-10 moles) were slightly but significantly decreased by isoproterenol (2 × 10^-7M) to a similar degree in NR and SHR. Tertatolol (3 X 10^-7M) 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 × 10^-7M) 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 × 10^-6M) 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^-7M). Our results show that the β-receptor agonist isoproterenol evokes comparable effects at prejunctional β-adrenoceptors in kidneys of NR and SHR; they also show that tertatolol is an inhibitor of pre- and postjunctional β-adrenoceptors in the renal circulation of the rat.

Tertatolol Preserves Renal Perfusion in Patients with Arterial Hypertension after Head Injury

“…These results are in agreement with those obtained in pharmacological trials both in intact hypertensive ani mals [14] and in isolated perfused kidney [19]. The mechanisms by which tertatolol can exert this antivasoconstrictive effect at the level of renal circulation remain to be clarified.…”

Renal Hemodynamic Effects of Tertatolol Compared with Those of Propranolol in the Conscious Dog

“…Finally, the (3-presynaptic blocking action of tertatolol observed in isolated rat kidney [20,22] may be taken into consideration. Blockade of presynaptic (3-receptors would inhibit the release of noradrenaline as well as the stimulating action of adrenaline and, therefore, reduce the vasoconstrictor nerve response [23].…”

MODULATION OF RENAL NORADRENALINE RELEASE BY PREJUNCTIONAL RECEPTOR SYSTEMS IN VITRO

“…1983). Moreover, in another recent study by Verbeuren and Herman (1986) the new P-adrenoceptor blocking drug tertatolol blocked the facilitatory effect of isoprenaline. Together these results suggest that activation of prejunctional 6-adrenoceptors on renal sympathetic nerves facilitates the release of noradrenaline.…”