Interaction of endothelin with renal nerves modulates kidney function in spontaneously hypertensive rats.

Background And Methods: We investigated kidney function, renal endothelin-1 concentration, prepro-endothelin-1 mRNA as well as endothelin receptor A and B mRNA expression and receptor properties in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with intact renal nerves and 7 days after renal denervation. In addition, responses of renal function to the non-selective ETA/ETB receptor blocker bosentan (10 mg/kg i.v. bolus injection) were studied.

Results: In SHR, renal papillary prepro-endothelin-1 mRNA expression, endothelin-1 tissue concentrations and endothelin receptor density were significantly lower than in normotensive rats. Renal denervation was associated with a decrease in papillary tissue prepro-endothelin-1 mRNA and in WKY rats also with a significant reduction in papillary endothelin-1 content without affecting ET receptor density. Bosentan did not alter renal blood flow or glomerular filtration rate but decreased urine flow rate in both intact normotensive and hypertensive rats, whereas it decreased urine sodium and potassium excretion only in intact WKY. Bosentan had no effects on renal function in renal denervated rats.

Conclusion: Since renal papillary endothelin-1 appears to counteract the fluid and sodium retaining effects of renal nerve activity, an impaired renal endothelin-1 synthesis in SHR may contribute to excessive sodium retention and thus to the pathogenesis of hypertension in SHR.