Renal hemodynamic control by endothelin and nitric oxide under angiotensin II blockade in man

To investigate whether endothelin-A receptors and nitric oxide modulate renal hemodynamics in man under angiotensin If receptor-1 blockade, 6 healthy volunteers, on a 240 mmol Na diet, underwent 4 separate renal hemodynamic measurements, in 3 of which endothelin-A blocker BQ-123 0.2 nmol (.) kg (.) min(-1) was infused for 90 minutes after pretreatment with either placebo, telmisartan 1 mg (.) kg (.) day(-1) for 3 days, or telmisartan as well, but with co-infusion of both BQ-123 and N-G-nitro-L-arginine methylester 0.5 mug (.) kg (.) min(-1). A fourth infusion was made with N-G-nitro-L-arginine methylester alone. No change followed infusion of either N-G-nitro-L-arginine methylester alone or BQ-123 alone. With BQ-123 after telmisartan, renal blood flow rose from 916 56 mL (.) min(-1) (.) 1.73 m(2) to 1047+/-51.2 (P<0.001), and renal vascular resistances fell from 89 7 mm Hg (.) min (.) L-1 to 74 4 (P<0.001). These changes were fully abolished by the co-infused N-G-nitro-L-arginine methylester. Infusion of BQ-123, devoid of renal hemodynamic effects at baseline, produces significant renal vasodilation when angiotensin If receptors are blocked, indicating an increasing renal hemodynamic role of endothelin-A-receptor activity. Because such a vasodilation is prevented by nonvasoconstricting microdoses of N-G-nitro-L-arginine methylester, nitric oxide-endothelin balance controls substantially renal hemodynamics under angiotensin 11 blockade. These findings are consistent with a rationale of the association of endothelin-A blockers with angiotensin II blockers or angiotensin-converting enzyme inhibitors in treating nitric oxide-deficient conditions such as arterial hypertension, heart failure, and chronic renal diseases.