RENAL VASODEPRESSOR MECHANISMS - THE MEDULLIPIN SYSTEM

Renal vasodepressor hormone: Medullipin I is the renomedullary vasodep ressor hormone secreted by the renomedullary interstitial cells of the renal papilla. It is conveyed to the liver where it is converted to i ts active form, medullipin II. Medullipin II is a vasodilator that sup presses sympathetic tone and causes diuresis and natriuresis. Its acti ons are opposite to those of angiotensin II. These are feedback contro l systems. The secretion and conversion of medullipin is related to th e cytochrome P-450 dependent enzyme system of kidney and liver. Defici ency of medullipin: A deficiency of medullipin is considered to contri bute to the pathogenesis of various hypertensive states. There are thr ee known causes for such a deficiency, (1) removal of renomedullary in terstitial cells by bilateral nephrectomy, renal surgical papillectomy , chemical papillectomy, papillary atrophy or necrosis; (2) decrease i n number and damage to renomedullary interstitial cells in accelerated experimental hypertension and malignant hypertension of humans; and ( 3) dysfunction of renomedullary interstitial cells as mediated by angi otensin II, by resetting of the effect of increased renal artery perfu sion pressure, by stimulation of the renal sympathetic nerve, by inhib ition of nitric oxide synthesis and possibly by inhibition of cyclo-ox ygenase. Secretion of medullipin I: The main factor influencing secret ion of medullipin I by the kidney appears to be the renal artery perfu sion pressure. Elevation of this pressure is attenuated by the presenc e of medullipin I in the renal venous effluent. Lowering the pressure below normal shuts off this secretion. This is opposite to the effects of perfusion pressure on renin secretion, as elevation shuts off reni n secretion while depression turns it on. Lowering blood pressure when given by mouth: Medullipin I lowers the blood pressure of spontaneous ly hypertensive rats when given by mouth without altering cardiac outp ut or heart rate, supporting its actions as a vasodilator that suppres ses sympathetic tone. This suggests that medullipin has a future as a therapeutic agent in human hypertension. Medullipin system in humans: Hypotension due to hypermedullipinemia has been described in a female who had a lipomedullipinoma in her remaining kidney that hypersecreted medullipin I autonomously.