Six patients in whom "essential hypertension" led to nephrosclerosis and kidney failure received kidney transplants from normotensive donors. After an average follow-up of 4.5 years, all were normotensive and had evidence of reversal of hypertensive damage to the heart and retinal vessels. These six patients, all of whom were black, and six control subjects matched for age, sex, and race were admitted to the General Clinical Research Center for 11 days for observation of their blood pressure and their responses to salt deprivation and salt loading. Mean arterial pressure (+/- S.E.M.) among the patients who had previously had essential hypertension was similar to that of the normal controls (92 +/- 1.9 vs. 94 +/- 3.9; P not significant), and both groups had similar responses to salt deprivation and salt loading. Thus, essential hypertension in human beings is shown to be similar to the hypertension seen in spontaneously hypertensive rats in that both can be corrected by transplantation of a kidney from a normotensive donor. This observation supports the concept of the primary of the kidney in causing essential hypertension.

No abstract

No abstract

Both the inhibition of renin release by sodium chloride and salt-sensitive hypertension have been attributed to sodium. We evaluated the contribution of chloride to these responses to sodium chloride. In the Sprague-Dawley rat, acute and chronic administration of sodium salts other than sodium chloride failed to suppress plasma renin activity, whereas renin was inhibited by both sodium chloride and by selective chloride (without sodium) loading. Plasma renin activity was stimulated by selective chloride depletion. Similarly, in humans, plasma renin activity was suppressed by sodium chloride but not by sodium bicarbonate infusion. In a preliminary study in the Dahl salt-sensitive rat, in contrast to sodium chloride loading, sodium bicarbonate loading failed to produce hypertension. Thus, both the renin and possibly the blood pressure responses to sodium chloride are dependent on chloride.

Maintenance of metabolic alkalosis generated by chloride depletion is often attributed to volume contraction. In balance and clearance studies in rats and humans, we showed that chloride repletion in the face of persisting alkali loading, volume contraction, and potassium and sodium depletion completely corrects alkalosis by a renal mechanism. Nephron segment studies strongly suggest the corrective response is orchestrated in the collecting duct, which has several transporters integral to acid-base regulation, the most important of which is pendrin, a luminal Cl/HCO 3 2 exchanger. Chloride depletion alkalosis should replace the notion of contraction alkalosis.