Different response of ANP secretion to adrenoceptor stimulation in renal hypertensive rat atria

Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An α₁-AR agonist, cirazoline increased ANP release with positive inotropism. These α₁-AR agonist-mediated responses were attenuated by the α_1A-AR antagonist, but not by the α_1B- or α_1D-AR antagonist. An α₂-AR agonist, guanabenz and clonidine increased ANP release with negative inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline ≫ phenylephrine = guanabenz ≫ clonidine. In contrast, a β-AR agonist, isoproterenol decreased ANP release with positive inotropism and these responses were blocked by the β₁-AR antagonist but not by the β₂-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both β₁- and β₂-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial β₁-AR mRNA level but not α_1A-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that α_1A- and β₁-AR oppositely regulate atrial ANP release and that atrial β₁-AR expression/function is impaired in renal hypertensive rats.