Adrenoceptor-mediated cardiac and vascular responses in genetically growth hormone-deficient rats

Abstract

This study has measured cardiovascular parameters, pharmacological responses to α and β-adrenoceptor agonists, and cardiac β-adrenoceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewis rats, normal Lewis rats and dwarf rats treated with GH (2mg/kg/day for 28 days). Dwarf rats showed a decreased mean blood pressure and heart rate but an increased ventricular weight relative to body weight when compared with age-matched normal Lewis rats. Positive chronotropic responses in vivo to the non-selective β-adrenoceptor agonist, isoprenaline, were unchanged in dwarf rats. The selective β 1-adrenoceptor agonist, noradrenaline, was less potent in isolated right atria from dwarf rats although maximal responses were unchanged. Basal force of contraction was greater in isolated cardiac muscles from dwarf rats than from normal rats. Maximal positive inotropic responses to both calcium chloride and noradrenaline were reduced in left atria but increased in left ventricular papillary muscles from dwarf rats. Responses to the α 1-adrenoceptor agonist, phenylephrine, were markedly increased in isolated cardiac tissues from dwarf rats. Maximal contractile responses of isolated thoracic aortic rings from dwarf rats to KCl (100 mM) and the α-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular β-adrenoceptor density measured by 125I-cyanopindolol binding was significantly increased in dwarf rats. Administration of GH (2 mg/kg/day for 28 days) reversed the altered responses in dwarf rats. We conclude that GH: (a) is required for the development of normal contractile capability of cardiac and vascular tissues; (b) regulates both β-adrenoceptors and α- and β-adrenoceptor-mediated responses; (c) differentially regulates atrial and ventricular responsiveness.