Renal hemohynamic 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)...
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Published in | Hypertension (Dallas, Tex. 1979) Vol. 39; no. 2; p. 715 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Baltimore
American Heart Association, Inc
01.02.2002
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Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0194-911X 1524-4563 |