Studies on the pathogenesis of spontaneous hypertension of rats

During the initial phase of hypertension, stroke-prone spontaneously hypertensive rats (spSHR) retain notably more sodium than normotensive Wistar-Kyoto rats (WKR) of the same age. Fractional sodium excretion and blood pressure rise with age, and sodium balance is in equilibrium at 4 months, whereas it becomes negative in advanced stages of hypertension. During the developmental phase of hypertension, plasma volume and blood volume of young spSHR are diminished despite sodium retention, indicating fluid depletion. Plasma sodium concentration is higher in spSHR than in WKR. Salt appetite and aldosterone secretion are reduced, whereas corticosterone secretion is enhanced in spSHR. It is supposed that, in spSHR, renal handling of sodium is primarily modified. This assumption is supported by the finding that spSHR in which an additional rise in blood pressure was elicited by unilateral renal artery stenosis neither show symptoms of acute sodium loss nor develop a compensatory hypertrophy of the contralateral kidney. The observation that renal denervation delays the development of hypertension in spSHR suggests the participation of the sympathetic system in the pathogenesis of genetic hypertension. Isolated perfused hindlimb preparations of young spSHR have a higher sensitivity to norepinephrine than do preparations from WKR. High sodium intake enhances and sodium restriction reduces the response of the hindlimb vascular bed to norepinephrine. Evidence is presented that early structural changes of the resistance vessels occur in spSHR at a time when blood pressure is only moderately elevated.