Effects of pheochromocytoma on cardiovascular alpha adrenergic receptor system

We have examined the in vivo consequences of prolonged stimulation of the cardiovascular alpha-adrenergic receptor system in a rat model harboring pheochromocytoma. New England Deaconess Hospital rats with transplanted pheochromocytomas developed systolic hypertension and their plasma norepinephrine concentrations were approximately 60-fold greater than controls. Alpha 1-adrenergic receptors were quantitated in hearts from controls and rats with transplanted pheochromocytoma using the alpha 1-receptor selective antagonist [3H]prazosin. Down-regulation of alpha 1-receptors was found in the hearts of pheochromocytoma rats (33.0 vs. 23.0 fmol/mg protein) without any significant change in the affinities of these receptors for the circulating catecholamine, norepinephrine. Furthermore, the responsiveness of the blood vessel to the alpha-adrenergic stimulation was assessed using in vitro contractile experiments. Aortic rings from pheochromocytoma animals showed an eight fold decrease in sensitivity (EC50) and a 74% decrease in maximal contractility (Emax) to norepinephrine as compared with controls. Similarly, mesenteric artery rings prepared from the same animals showed a five fold loss of EC50 but no decrease in Emax to phenylephrine as compared with controls. In addition, serotonin EC50 and Emax of these mesentery preparations remained unaltered. Coupled with our previous findings [9], the present study suggests that rats with pheochromocytoma secreting large amounts of norepinephrine provide a valuable model system for studying in vivo desensitization of the cardiovascular alpha-receptor systems as well as the beta-adrenergic receptor system.