Endothelin-A blockade attenuates systemic and renal hemodynamic effects of L-NAME in humans.
Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N(G)-nitro-L-arginine methyl ester (L-NAME) 3.0 mg. kg(-1). min(-1) or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol. kg(-1). min(-1) or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% (P<0.001 versus b) in period 1, to 9.9% (P<0. 001) in period 2 with L-NAME, and by 3.3% (P<0.01) to 6.6% (P<0.001) with L-NAME plus BQ (P=NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P<0.001) but not with coinfused BQ (2. 1%; P=NA versus b, P=0.005 versus L-NAME alone). RBF declined by 12. 2% (P<0.001) to 18.3% (P<0.001) with L-NAME and by 4.6% (P<0.005) to 8.2% (P<0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ (P<0.05 in period 1 and P<0.02 in period 2). Blunted changes were also seen for RVR (P<0.005 in period 1 and P<0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.
Montanari
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A
Istituto di Patologia Medica and Istituto di Semeiotica Medica, University of Parma, Italy. montalbr@unipr.it
Biggi
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A
Carra
N
N
Fasoli
E
E
Calzolari
M
M
Corsini
F
F
Perinotto
P
P
Novarini
A
A
D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology; D008094:Lithium / Q000652:urine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D044022:Receptor, Endothelin A; D012964:Sodium / Q000652:urine; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D009573:Nitrites; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; D009569:Nitric Oxide; D008094:Lithium; D012964:Sodium; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester