Effects of Tertatolol on the Responsiveness of Isolated Femoral, Mesenteric, and Renal Resistance Arteries to Adrenergic Stimuli

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Abstract
We evaluated effects of the β-adrenoceptor antagonist tertatolol on responses of resistance arteries to isoproterenol and phenylephrine and compared them with those of propranolol. The experiments were performed in femoral, mesenteric, and renal resistance arteries that had been isolated from adult Wistar-Kyoto rats, chemically sympathectomized and mounted for recording of contractile reactivity in vitro. In renal resistance arteries that had been pretreated with phenoxybenzamine, isoproterenol did not affect contractile responses to potassium. Under these conditions, isoproterenol induced relaxation in mesenteric resistance arteries. Low concentrations of both SR-tertatolol and SR-propranolol shifted concentration-response curves for isoproterenol to the right. Affinity for competitive β-adrenergic antagonism did not differ between both agents. Unlike SR-propranolol, SR-tertatolol reduced maximal relaxing responses to isoproterenol. As compared with R-tertatolol, S-tertatolol was 100 times less potent as a competitive β-adrenergic antagonist and failed to affect maximal relaxing responses to isoproterenol. In femoral, mesenteric, and renal resistance arteries preconstricted by phenylephrine, concentrations of SR-tertatolol >1 μM induced relaxation. This relaxing effect did not differ between SR-tertatolol and SR-propranolol or between S-tertatolol and R-tertatolol. These data indicate that in resistance arteries tertatolol is a stereoselective β-adrenoceptor antagonist that exhibits both a competitive and a noncompetitive mechanism of action. In addition, high concentrations of tertatolol relax resistance arterial smooth muscle. This effect was neither stereoselective nor selective for the renal vascular bed and was also observed with propranolol.