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(Hypertension. 2002;39:715.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Renal Hemodynamic Control by Endothelin and Nitric Oxide Under Angiotensin II Blockade in Man

Alberto Montanari; Nicoletta Carra; Patrizia Perinotto; Veronica Iori; Elena Fasoli; Almerina Biggi; Almerico Novarini

From the Dipartimento di Scienze Cliniche e Sperimentale, University of Parma, Italy.

Correspondence to Alberto Montanari, MD, Dipartimento di Scienze Cliniche, Via Gramsci 14, I-43100 Parma, Italy. E-mail montalbr{at}unipr.it

To investigate whether endothelin-A receptors and nitric oxide modulate renal hemodynamics in man under angiotensin II 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 µg · 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 m² 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 II 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 II 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.

Key Words: angiotensin II • nitric oxide • endothelin • kidney • hemodynamics • L-NAME • receptors, endothelin

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