The effect of beta adrenergic blockade on pulmonary hypertension, right ventricular hypertrophy and polycythaemia, induced in rats by intermittent high altitude hypoxia.

Abstract

Adult male rats were used to study the effect of a beta blocking agent on pulmonary hypertension and right ventricular hypertrophy induced by intermittent high altitude (IHA) hypoxia (8 hr daily, 5 days a week, stepwise up to the simulated altitude of 7000 m). Trimepranol was injected subcutaneously in a single dose of 10 mg/kg/b.w. one hour before each IHA exposure. Administration of the beta blocking drug caused significant changes of haematocrit values even in animals kept under normoxic conditions. The initial deep decrease was followed by a slow return to control values; prolongation of treatment led to a further significant decrease of the haematocrit curve. The polycythaemic response of IHA-exposed and Trimepranol-treated animals was, therefore, significantly less pronounced as compared with the hypoxic non-treated group. Administration of Trimepranol to IHA-exposed rats significantly decreased the values of right ventricular systolic and mean pressure, right ventricular hypertrophy as well as the degree of muscularization of pulmonary arteries. It may be assumed that the protective effect of Trimepranol is due to a) changes in pulmonary vascularization, b) reduction of polycythaemia, and c) lower cardiac output, induced by the negative inotropic and chronotropic effect of this drug.