ADRENOCEPTOR-MEDIATED CARDIAC AND VASCULAR-RESPONSES IN GENETICALLY GROWTH HORMONE-DEFICIENT RATS

This study has measured cardiovascular parameters, pharmacological res ponses to alpha- and beta-adrenoceptor agonists, and cardiac beta-adre noceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewi s rats, normal Lewis rats and dwarf rats treated with GH (2 mg/kg/day for 28 days). Dwarf rats showed a decreased mean blood pressure and he art rate but an increased ventricular weight relative to body weight w hen compared with age-matched normal Lewis rats. Positive chronotropic responses in vivo to the non-selective beta-adrenoceptor agonist, iso prenaline, were unchanged in dwarf rats. The selective beta1-adrenocep tor agonist, noradrenaline, was less potent in isolated right atria fr om dwarf rats although maximal responses were unchanged. Basal force o f contraction was greater in isolated cardiac muscles from dwarf rats than from normal rats. Maximal positive inotropic responses to both ca lcium chloride and noradrenaline were reduced in left atria but increa sed in left ventricular papillary muscles from dwarf rats. Responses t o the alpha1-adrenoceptor agonist, phenylephrine, were markedly increa sed in isolated cardiac tissues from dwarf rats. Maximal contractile r esponses of isolated thoracic aortic rings from dwarf rats to KCl (100 mM) and the alpha-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular beta-ad renoceptor density measured by I-125-cyanopindolol binding was signifi cantly increased in dwarf rats. Administration of GH (2 mg/kg/day for 28 days) reversed the altered responses in dwarf rats. We conclude tha t GH: (a) is required for the development of normal contractile capabi lity of cardiac and vascular tissues; (b) regulates both beta-adrenoce ptors and alpha- and beta-adrenoceptor-mediated responses; (c) differe ntially regulates atrial and ventricular responsiveness.