The mechanism of the augmentation of the pressor response to angiotensinamide and to adrenaline by β-adrenoceptor blocking agents in the rat

Summary

In normal or nephrectomized rats, unanaesthetized or anaesthetized with urethane i.v., D,L-propranolol (0.25 or 0.5 mg/kg) or practolol (2.5 or 5 mg/kg) provoked a short-lasting peak of blood pressure (BP) which was abolished by adrenalectomy. D-propranolol (0.25 mg/kg) or lidocaine (0.25 mg/kg) caused a similar peak which was abolished by phentolamine (0.5 mg/kg). This initial pressor peak appears to be due to an enhanced release of adrenaline and/or of noradrenaline from the adrenal medulla. Acute pressor responses to D,L-propranolol and practolol, but not to D-propranolol or lidocaine, were followed by an elevation of base line BP. The pressor response to β-blocking agents appears to be due to a depression of the continuous vasodilator effect of endogenous adrenaline. In spite of an increase in base line BP, D,L-propranolol or practolol enhanced pressor responses to single injections of 3–25 ng/kg angiotensinamide or 0.4–1.5 ng/kg adrenaline, or to continuous infusion of 45 ng/kg · min angiotensinamide.

Pentolinium did not interfere with the effects of D,L-propranolol. Pentobarbital anaesthesia abolished the pressor responses to D,L-propranolol but not its propensity to enhance the pressor responses to angiotensinamide or to adrenaline. D,L-propranolol failed to increase pressor responses to angiotensinamide in adrenalectomized, prednisolone-substituted rats. Since the pressor responses to angiotensinamide are partially mediated by release of catecholamines from the adrenal medulla, the data are interpreted as indicating that β-adrenoceptor blocking agents enhance pressor effects of adrenaline and/or noradrenaline by suppressing their vasodilator effects.