Effect of pheochromocytoma and hypophysectomy on blood pressure and catecholamines in NEDH rats.

Abstract

The New England Deaconess Hospital (NEDH) rat provides a valuable model with which to study pheochromocytoma (P); 59% of male rats 700 to 900 days old and 81% of those 900 days or older developed spontaneous P. One transplantable P (P259), when implanted into other NEDH rats, markedly increased plasma norepinephrine and dopamine as well as blood pressure, and usually caused death within 4 weeks. Even without P, about 83% of NEDH rats became hypertensive by 131/2 weeks of age and remained moderately hypertensive until 2 years of age when some animals developed spontaneous P and hypertension became severe. Whether a common mechanism is responsible for early appearance of hypertension and later development of P remains to be determined. Hypophysectomized NEDH rats remained normotensive or slightly hypotensive despite marked elevations of plasma norepinephrine and dopamine caused by P259 implantation; furthermore, survival was prolonged to 3 months. Catecholamine concentrations in plasma and RBC were usually quite similar, indicating that red blood cells play a significant role in inactivating circulating catecholamines. Unlike the normal adrenal, P259 in NEDH rats contains mainly norepinephrine and dopamine with little epinephrine; it appears that P259 is deficient in the enzyme phenylethanolamine-N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. Why hypophysectomy prevents hypertension and prolongs life in rats with P259 implants is unclear; adrenal cortical and thyroid deficiency may play a role. Preliminary observations indicate that hypophysectomy can prevent spontaneous development of P in NEDH rats.