Reduction by beta-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat.
1. The study was undertaken to assess the role of beta-adrenoceptors in the induction of compensatory cardiac hypertrophy in an in vivo model. 2. In the rat, exposure to severe hypoxia (6% inspired oxygen for 8 h day) caused a 51% increase in right heart weight and a 75% increase in haematocrit. 3. The hypoxia-induced right ventricular hypertrophic response was reduced by 65% by oral treatment with a high dose of the non-selective beta-adrenoceptor antagonist, propranolol (80 mg kg-1 body weight); the drug treatment caused only a minor reduction (6%) in secondary polycythaemia. 4. With a less severe degree of hypoxia (7% inspired oxygen) there was only minimal secondary polycythaemia (+15%), and a lesser degree of compensatory right ventricular hypertrophy in untreated rats (+33%). 5. Treatment with the beta 1-adrenoceptor antagonist, atenolol, in a dose of 80 mg kg-1 body weight abolished right ventricular hypertrophy in response to 7% inspired oxygen, without affecting haematocrit and caused a small reduction in the ratio of heart weight to body weight in normoxic rats. 6. The results show that the effect of propranolol on hypoxic right ventricular hypertrophy is not secondary to any effect on secondary polycythaemia as has previously been suggested and that a marked reduction of compensatory cardiac hypertrophy can be obtained by a beta 1-selective adrenoceptor antagonist. Thus these findings support the view that noradrenaline released from cardiac sympathetic nerve terminals exerts a trophic effect on myocardial cells and demonstrates that in vivo, this trophic effect can be reduced by beta 1-adrenoceptor blockade.
Ostman-Smith
I
I
Department of Cardiovascular Medicine and Paediatrics, John Radcliffe Hospital, Oxford.
D000284:Administration, Oral; D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D005260:Female; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications* / Q000188:drug therapy; D011433:Propranolol / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D001262:Atenolol; D011433:Propranolol