ROLE OF NITRIC-OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION

1. Nitric oxide (NO) has been implicated as an important controller in the short- and long-term regulation of arterial pressure, Studies per formed in our laboratory have demonstrated that chronic intravenous ad ministration of the NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) selectively decreases renal medullary blood how causes sodium and water retention and leads to hypertension, 2. To determine the importance of the renal medullary effects in this model of hyperte nsion, further studies were conducted to examine the influence of sele ctive stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique cath eter to directly infuse into the renal medullary interstitial space, s timulation (bradykinin or acetylcholine) or inhibition (L-NAME) of ren al medullary NO selectively increased or decreased renal medullary blo od flow. 3. The changes in medullary flow in these experiments were as sociated with parallel changes in sodium and water excretion independe nt of alterations in renal cortical blood flow or glomerular filtratio n rate, 4. Studies were then undertaken to examine the long-term effec ts of selective NO inhibition in the renal medulla on cardiovascular h omeostasis. Chronic infusion of L-NAME directly into the renal medulla ry interstitial space of uninephrectomized Sprague-Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L-NAME infusion period, The decrease in medullary blood flow was associated with retention of sodium and the developmen t of hypertension and the effects were reversible, 5. The data reviewe d indicate that NO in the renal medulla has a powerful influence on fl uid and electrolyte homeostasis and the control of blood pressure.