Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats

Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats.BackgroundAs yet, there are only limited data available on the exact role of endothelin (ET) acting through endothelin-A (ETA) receptors in renal sodium and water regulation and the potential functional implications of an interaction of the renal ET system with renal nerves in normotensive and spontaneously hypertensive rats.MethodsExperiments were carried out in 64 male conscious spontaneously hypertensive rats and in 56 normotensive Wistar-Kyoto (WKY) rats. Bilateral renal denervation (BRD) was performed in 32 spontaneously hypertensive rats and 28 WKY rats 7days before the experiments. The ETA receptor antagonist, BQ-123 (16.4nmol/kg.min intravenously) or the endothelin-B (ETB) receptor antagonist, BQ-788 (25nmol/kg.min intravenously) were infused at a rate of 25 μL/min for 50 minutes.ResultsRenal papillary ET-1 concentration in intact spontaneously hypertensive rats was 67.8% lower than in intact WKY rats (154 ± 40 fmol/mg protein vs. 478 ± 62 fmol/mg protein, P < 0.01). BRD decreased papillary ET-1 by 73.5% in WKY rats to 127 ± 19 fmol/mg protein (P < 0.001), but had no effect in spontaneously hypertensive rats (122 ± 37 fmol/mg protein). BRD, BQ-123, or BQ-788 did not affect glomerular filtration rate (GFR) or renal blood flow (RBF) in any of the groups. In intact WKY, BQ-123 decreased urine flow rate (V) from 4.65 ± 0.44 μL/min.100g body weight to 2.44 ± 0.35 μL/min.100g body weight (P < 0.01), urinary excretion of sodium (UNaV) from 238.2 ± 27.4 to 100.2 ± 17.0 (P < 0.01) and potassium (UKV) from 532.1 ± 62.6nmol/min.100g body weight to 243.0 ± 34.2nmol/min.100g body weight (P < 0.001), whereas BQ-788 decreased only V and UNaV. In renal denervated WKY, BQ-123 or BQ-788 did not alter V, UNaV, or UKV. In intact spontaneously hypertensive rats BQ-123 but not BQ-788 decreased V from 3.94 ± 0.48 μL/min.100g body weight to 2.55 ± 0.44 μL/min.100g body weight (P < 0.05). In renal denervated spontaneously hypertensive rats neither BQ-123 nor BQ-788 affected V, UNaV, or UKV.ConclusionAn interaction between ET and renal nerves is involved in the control of renal function. Moreover, renal nerves participate in the regulation of ET-1 production within the kidney. Finally, decreased synthesis of ET-1 in the renal papilla of spontaneously hypertensive rats may contribute to development and/or maintenance of hypertension due to modulation of renal excretory function