Adrenoceptor-mediated cardiac and vascular responses in genetically growth hormone-deficient rats.
This study has measured cardiovascular parameters, pharmacological responses to alpha- and beta-adrenoceptor agonists, and cardiac beta-adrenoceptor characteristics in growth hormone (GH)-deficient (dwarf) Lewis rats, normal Lewis rats and dwarf rats treated with GH (2 mg/kg/day for 28 days). Dwarf rats showed a decrease 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 beta-adrenoceptor agonist, isoprenaline, were unchanged in dwarf rats. The selective beta 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 alpha 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 alpha-adrenoceptor agonist, noradrenaline, were markedly reduced compared to responses in normal rats. Left ventricular beta-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 beta-adrenoceptors and alpha- and beta-adrenoceptor-mediated responses; (c) differentially regulates atrial and ventricular responsiveness.
Department of Physiology and Pharmacology, University of Queensland, Australia.
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Brown
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Wyse
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Sernia
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009929:Organ Size; D051381:Rats; D011917:Rats, Inbred Lew / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000032:analysis*
D011943:Receptors, Adrenergic, beta; D013006:Growth Hormone