Captopril improves hypertension and cardiomyopathy in rats with pheochromocytoma.

Abstract

Hypertension and cardiomyopathy are prominent findings in humans and rats harboring pheochromocytomas, tumors that can secrete enormous quantities of catecholamines. We have previously found that a-and /J-adrenergic receptor antagonists may ameliorate the hypertension and cardiomyopathy found in New England Deaconess Hospital rats implanted with pheochromocytoma. The present studies were designed to determine the possible action of the angiotensin converting enzyme inhibitor captopril on these changes in rats harboring pheochromocytomas. Rats were implanted with transplantable pheochromocytomas and treated with captopril dissolved in the drinking water (1 mg/ml) for 4 -6 weeks. Systolic blood pressure was monitored by using the tail-cuff technique. In the rats with pheochromocytoma, blood pressure progressively increased to 184±3 mm Hg after the tumor was implanted. However, in rats with pheochromocytoma treated with captopril in the drinking water before the development of hypertension, blood pressure did not increase (137±3 mm Hg). In rats with pheochromocytoma with established hypertension, captopril normalized the systolic blood pressure. Plasma norepinephrine was markedly elevated to a similar extent in both groups compared with unimplanted control rats. Plasma renin activities were slightly lower in rats with pheochromocytoma compared with unimplanted control rats. Treatment with captopril of rats with pheochromocytoma did not modify contraction of isolated rings of thoracic aorta exposed in vitro to either phenylephrine or angiotensin H, Treatment with captopril markedly attenuated the cardiomyopathy induced by pheochromocytoma. These results demonstrate that captopril prevents the development of hypertension despite markedly elevated concentrations of catecholamines. In addition, captopril attenuates catecholamine-induced cardiomyopathy in pheochromocytoma. To what extent these effects of captopril reflect actions on local renin-angiotensin systems or other mechanisms requires further study. (Hypertension 1990;15:210-215) P heochromocytoma is a rare but dramatic cause of human hypertension. 1 These tumors typically secrete large quantities of norepinephrine. Hypertension in patients with pheochromocytoma may be severe; also, many patients with this tumor have been found to have a cardiomyopathy that is highly suggestive of lesions induced by cateFrom the