Blockade of β-adrenoceptors enhances cAMP signal transduction in vivo

Abstract

The aim of this study was to determine whether the blockade of β-adrenoceptors would enhance cAMP-mediated signal transduction processes in vivo. The administration of the membrane permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP, 10 μmol/kg, i.v.) produced an increase in heart rate (+27±2%, P<0.05), a fall in mean arterial blood pressure (−21±3%, P<0.05) and falls in hindquarter (−12±3%, P<0.05) and mesenteric (−32±3%, P<0.05) vascular resistances in pentobarbital-anesthetized rats. The β-adrenoceptor antagonist, propranolol (1 mg/kg, i.v.) lowered heart rate (−12±3%, P<0.05) but did not affect mean arterial blood pressure or vascular resistances. The tachycardia, hypotension and vasodilation produced by 8-CPT-cAMP were exaggerated after administration of propranolol ( P<0.05 for all comparisons). The nitric oxide-donor, sodium nitroprusside (2 μg/kg, i.v.), produced falls in mean arterial blood pressure and vascular resistances of similar magnitude to those produced by 8-CPT-cAMP. These sodium nitroprusside-induced responses were unaffected by propranolol ( P<0.05 for all comparisons). Sodium nitroprusside also produced a minor increase in heart rate (+5±1%, P<0.05) which was abolished by propranolol. These findings suggest that 8-CPT-cAMP directly increases heart rate and that blockade of β-adrenoceptors enhances the potency of cAMP within the heart and vasculature.