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 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 center dot 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 microg.kg center dot 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 center dot min(-1) center dot 1.73 m(2) to 1047 +/- 51.2 (P<0.001), and renal vascular resistances fell from 89 +/- 7 mm Hg center dot min center dot 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.
Montanari
Alberto
A
Dipartimento di Scienze Cliniche e Sperimentale, University of Parma, Italy. montalbr@unipr.it
Carra
Nicoletta
N
Perinotto
Patrizia
P
Iori
Veronica
V
Fasoli
Elena
E
Biggi
Almerina
A
Novarini
Almerico
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D000077333:Telmisartan
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D016232:Endothelins; D000804:Angiotensin II; D009569:Nitric Oxide; D000077333:Telmisartan