Prejunctional beta-adrenoceptors in the isolated perfused rat kidney: a comparative study of the beta-blockers tertatolol and propranolol.
The interaction of the beta-blocker tertatolol with the prejunctional beta-adrenoceptors of the rat renal vasculature was examined. In isolated Tyrode-perfused rat kidneys isoproterenol (5 x 10(-7) M to 2 x 10(-6) M) slightly decreased the pressor responses to noradrenaline (0.5 nmol), but markedly increased those to electrical stimulation (6 Hz). Tertatolol at 3 x 10(-7) M inhibited both effects of isoproterenol. Electrical stimulation (6 Hz) caused an overflow of intact 3H-noradrenaline from kidneys previously labelled with the 3H-transmitter; this stimulation-induced release was augmented by isoproterenol. Also this effect of isoproterenol was prevented by 3 x 10(-7) M of tertatolol. In different groups of rat kidneys labelled with 3H-noradrenaline, isoproterenol (5 x 10(-7) M) augmented the stimulation (1 Hz), induced 3H overflow and this increased transmitter output was concentration-dependently inhibited by tertatolol and propranolol; from the IC50 values it was calculated that tertatolol was 16 times more potent than propranolol. Even at concentrations up to 10(-5) M, neither tertatolol nor propranolol significantly altered the basal and stimulation-induced transmitter release from the rat kidneys. From the data we conclude that tertatolol is a powerful inhibitor of the prejunctional beta-adrenoceptors in the renal circulation of the rat. Stimulation of these receptors by beta-agonists not only enhances transmitter release but also increases the pressor responses induced by electrical stimulation.
Verbeuren
T J
TJ
Fondax, Groupe de Recherches Servier, Puteaux, France.
Zonnekeyn
L L
LL
Prost
J F
JF
Herman
A G
AG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010477:Perfusion; D011412:Propanolamines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012079:Renal Circulation / Q000187:drug effects; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013876:Thiophenes; D011433:Propranolol; C005632:tertatolol; D007545:Isoproterenol; D009638:Norepinephrine