Hypoxic cardiac hypertrophy is not inhibited by cardioselective or non‐selective beta‐adrenoceptor antagonists.

Abstract

SUMMARY1. Young rabbits, eight at a time, were exposed to more than 170 hr of hypoxia (02 at 70-80 torr) at atmospheric pressure during 9-11 days.2. The animals were injected twice daily with doses of fl-blockers up to the highest used in human therapy, or with an equivalent volume of saline. These controls were litter mates of the treated rabbits.3. In comparison with untreated normoxic rabbits of similar age, the hypoxia induced highly significant mean increases in right ventricular dry weight (+ 57 %, controls; + 55 % treated).4. In each group, the same degree of hypertrophy was induced in the treated and control animals, irrespective of whether the drug used was a non-selective ,f-blocker (propranolol) or a cardioselective drug (atenolol).5. The right atria were also hypertrophied, though not as much as the right ventricles.6. In all the hypertrophied tissues the water content was increased. 7. No significant change was observed in the dry weight or water content of the left ventricles of treated or control animals.

Effects of Adrenoceptor Blockade on Cardiac Hypertrophy and Myocardial Phospholipids

“…Subsequent studies employing adrenal demedullation (8), a-or P-adre-noceptor blockade ( 1 ), or chemical sympathectomy ( 17) have generally supported the view that adrenergic intervention has little or no effect on the hypertrophic response to pressure overload. Similarly, sympathectomy or P-adrenoceptor blockade does not prevent cardiac hypertrophy in spontaneously hypertensive rats (24)(25)(26), renal hypertensive rats (27), or rabbits subjected to hypoxia (28,29).…”

Hemodynamic versus adrenergic control of cat right ventricular hypertrophy.

“…First, increasing the length of isolated, denervated cardiac tissue has the immediate effect of increasing protein synthesis (1). Second, either during j3-adrenoceptor blockade (2) or after sympathectomy (3), chronic hypoxia, which may result in numerous changes including pulmonary arterial hypertension, causes right ventricular hypertrophy. Third, we have found recently that changing myocardial load, without selective changes either in cardiac innervation or in catecholamine content, results in marked, reversible alterations in cardiac structure and function (4,5).…”

Hypoxia‐induced cardiac hypertrophy in rabbits treated with verapamil and nifedipine

“…Blood viscosity rises logarithmically as a function of haematocrit (discussed in detail by Vaughan Williams & Dukes, 1983), and the 46% increase in Hct may have greatly increased the work load causing the left ventricular hypertrophy, and a right-sided hypertrophy disproportionate to the total duration of hypoxia. It is of interest that in another study (Dennis & Vaughan Williams, 1982) in which rabbits were exposed to hypoxia with two intermittent periods of normoxia daily, as in the present series, there was no left-sided hypertrophy, and the right ventricular and atrial hypertrophies were 57% and 32% respectively.…”

“…It is probable that many causative and permissive factors are concerned in stimulating cardiac hypertrophy but in recent years it has been suggested that release of adrenaline and/or some other trophic factor from sympathetic nerves provides the final link in the chain (Ostman-Smith, 1981). If this were so, treatment of post-infarction patients with P-blockers could inhibit compensatory hypertrophy of the surviving myocardium, but in a previous paper (Dennis & Vaughan Williams, 1982) it was shown that much larger than clinical doses of the P-blockers atenolol (cardio-selective) and propranolol (non-selective) did not inhibit the right ventricular hypertrophy induced by hypoxia. The hypertrophy could, of course, have been triggered by some non-adrenergic influence released from sympathetic nerve endings and this possibility could only be tested by destruction of the nerves themselves.…”

“…Verapamil, nifedipine and other drugs loosely termed 'calcium antagonists' are used for the treatment of angina pectoris and hypertension, sometimes in association with ischaemic heart disease. It seemed worthwhile, therefore, to investigate whether verapamil or nifedipine could inhibit hypoxicallyinduced hypertrophy, employing the methods already developed to study the effects of antisympathetic agents (Dennis & Vaughan Williams, 1982;Vaughan Williams & Dukes, 1983 Six litters containing six rabbits were used. Three groups of rabbits, each group containing animals from two litters, were exposed eight at a time to prolonged periods of hypoxia.…”