Affiliation:
1. From the Dipartimento di Scienze Cliniche e Sperimentale, University of Parma, Italy.
Abstract
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 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 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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
15 articles.
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