Alterations in Renal Medullary Hemodynamics and the Pressure-Natriuretic Response in Genetic Hypertension

The concept that the kidney plays a major role in the long-term control of arterial pressure is based on the pressure-natriuretic response. According to this hypothesis, hypertension can only develop when the relationship between sodium excretion and arterial pressure is altered. Transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic forms of hypertension in the spontaneously hypertensive rat (SHR) and in the Dahl salt-sensitive (S) rat. Nonetheless, the factors responsible for “resetting the kidney in hypertension” remain unknown. We have reported that the pressure-natriuretic relationships of SHR and Dahl S rats of the Brook-haven and Rapp strains are shifted toward higher pressures prior to the development of the disease. Papillary blood flow is also reduced in very young “prehypertensive” SHR. Recent studies on the mechanism of pressure-diuresis indicate that it is mediated by inhibition of sodium reabsorption in the proximal tubule and/or thin descending limb of Henle of deep nephrons. It is also associated with changes in renal interstitial pressure and the pressure and flow in the vasa recta circulation. These observations suggest that an elevation in renal medullary vascular resistance may be responsible for shifting the pressure-natriuresis relationship toward higher pressures in hypertension. The alterations in renal medullary hemodynamics in the SHR may be secondary to an elevation in renal sympathetic tone, a deficiency in the kallikrein-kinin system, and/or an elevated production of vasoconstrictor metabolites of arachidonic acid. In prehypertensive Dahl S rats papillary blood flow is not reduced. Therefore, changes in the control of renal tubular function by the renin-angiotensin, kallikrein-kinin and/or renal eicosanoid systems may be responsible for resetting the relationship between sodium excretion and arterial pressure in these animals. Am J Hypertens 1990;3:893-900