Renal functional, not morphological, abnormalities account for salt sensitivity in Dahl rats.

Background: The kidney's role in the pathogenesis of salt-induced hypertension remains unclear. However, it has been suggested that inherited morphological renal abnormalities may cause hypertension. We hypothesized that functional, not morphological, derangements in Dahl salt-sensitive rats' kidneys cause NaCl retention that leads to hypertension accompanied by renal pathologic changes and proteinuria.

Method: We studied hemodynamic, renal morphologic, and biochemical differences in Dahl salt-resistant and Dahl salt-sensitive rats fed low (0.05-0.23% NaCl) or elevated (1% NaCl) salt diets.

Results: We found similar hemodynamics, equal numbers of glomeruli, normal renal medullary interstitial cells and their osmiophilic granules, and cortical morphology in normotensive Dahl salt-resistant and Dahl salt-sensitive rats fed low dietary salt. Furthermore, aldosterone secretion, caused by angiotensin II infusion in normotensive rats fed 0.23% NaCl, was significantly less in Dahl salt-sensitive than Dahl salt-resistant rats. Increasing NaCl to 1% caused renal vasoconstriction without changing cyclic GMP excretion in Dahl salt-sensitive rats; in Dahl salt-resistant rats, cyclic GMP increased markedly and renal vascular resistance remained unchanged. On 1% NaCl for 9 months, Dahl salt-sensitive rats developed marked hypertension, severe renal vasoconstriction, glomerulosclerosis, tubulointerstitial abnormalities, and marked proteinuria; hypertension resulted from increased total peripheral resistance, as occurs in essential hypertensive humans. No hemodynamic or renal pathologic changes occurred in Dahl salt-resistant rats, and proteinuria was minimal.

Conclusion: We conclude that renal functional, not morphological, abnormalities cause salt sensitivity in Dahl rats.