Role of the sympathetic nervous system in the maintenance of hypertension in rats harboring pheochromocytoma.
Hypertension due to pheochromocytoma is generally considered to be a straightforward, direct consequence of the elevated concentrations of circulating catecholamines. However, clonidine, a centrally acting antihypertensive drug, has been reported to lower blood pressure in patients with pheochromocytoma, suggesting the possibility that the sympathetic nervous system is involved in the maintenance of hypertension in this disease. We have investigated this possibility in New England Deaconess Hospital rats harboring a transplantable pheochromocytoma that secretes norepinephrine and dopamine. Both clonidine and chlorisondamine, a ganglionic blocker, markedly decreased blood pressure in tumor-bearing rats. However, in other rats made acutely hypertensive with a norepinephrine infusion, neither clonidine nor chlorisondamine decreased blood pressure. This result indicates that in an acute model of hypertension, where baroreflex mechanisms have likely withdrawn sympathetic tone, neither clonidine nor chlorisondamine had nonspecific antihypertensive effects. A central nervous system site of action for the antihypertensive effect of clonidine in the rats harboring pheochromocytoma was suggested by the observation that the opiate antagonist naloxone both reversed and prevented clonidine's effect on blood pressure. Prazosin and yohimbine were utilized to determine the respective contributions of alpha-1 and alpha-2 adrenergic receptors in the maintenance of hypertension in rats harboring pheochromocytoma. Both drugs markedly lowered blood pressure in these rats. Our data suggest that both the sympathetic nervous system and circulating catecholamines are involved in the maintenance of hypertension due to pheochromocytoma.
D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D002714:Chlorisondamine / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology*; D009270:Naloxone / Q000494:pharmacology; D010673:Pheochromocytoma / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D009270:Naloxone; D002714:Chlorisondamine; D003000:Clonidine