Reduction by β-adrenoceptor blockade of hypoxia-induced right heart hypertrophy in the rat

摘要

1 The study was undertaken to assess the role of β-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 β-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 β_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 β_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 β_1 -adrenoceptor blockade.