THE RENAL MEDULLA AND HYPERTENSION

We review evidence supporting the conclusion that renal dysfunction un derlies the development of all forms of hypertension in humans and exp erimental animals. Indexes of global renal function are generally norm al in the early stages of most genetic forms of hypertension, but rena l function is clearly impaired in long-established hypertension. Studi es in our laboratory over the past decade summarized below have establ ished that the renal medulla plays an important role in sodium and wat er homeostasis and in the long-term control of arterial pressure. Deve lopment of implanted optical fibers for measurement of cortical and me dullary blood flows with laser-Doppler flowmetry and techniques for de livery of vasoactive compounds into the medullary interstitial space e nabled us to examine determinants of medullary flow (nitric oxide, atr ial natriuretic peptides, kinins, eicosanoids, vasopressin, renal symp athetic nerves, etc). We have shown in spontaneously hypertensive rats that the initial changes of renal function begin as a reduction of me dullary blood flow in the absence of changes of cortical flow. Long-te rm medullary interstitial infusion of captopril, which preferentially increased medullary blood flow, resulted in a lowering of arterial pre ssure. In normal Sprague-Dawley rats, selective reduction of medullary flow with medullary interstitial or intravenous infusion of small amo unts of N-G-nitro-L-arginine methyl ester resulted in hypertension. Th ese and other studies we review show that although blood flow to the i nner renal medulla comprises less than 1% of the total renal blood flo w, changes in flow to this region can have a major effect on sodium an d water homeostasis and on the long-term control of arterial blood pre ssure.