Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs.
The renal effects of the nitric oxide (NO) synthase inhibitor nitro-L-arginine methyl ester (L-NAME) were investigated in conscious dogs undergoing sustained water diuresis and replacement of urinary sodium losses. Experiments were performed with and without additional extracellular volume expansion (isotonic saline, 2% body wt). L-NAME (10 microg. kg(-1). min(-1)) infused during water diuresis decreased urine flow (2.5 +/- 0.2 to 1.5 +/- 0.3 ml/min), free water clearance (1.9 +/- 0.2 to 1.0 +/- 0.2 ml/min), and sodium excretion (4.0 +/- 1.7 to 2.1 +/- 0.6 micromol/min). Arterial blood pressure increased from 112 +/- 2 to 126 +/- 3 mmHg, but creatinine clearance did not measurably change. Plasma endothelin and vasopressin concentrations and plasma renin activity (PRA) were unchanged. Urinary endothelin concentration increased (3.4 +/- 0.8 to 6.2 +/- 1.7 pg/ml), but the excretion rate remained constant. L-Arginine infusion (0.6 mg. kg(-1). min(-1)) along with L-NAME abolished the renal effects but not the blood pressure increase. Volume expansion increased urine flow (2.5 +/- 0.4 to 5.7 +/- 0.5 ml/min) and sodium excretion (3.8 +/- 1.6 to 76.5 +/- 14.5 micromol/min). L-NAME attenuated the renal effects of volume expansion: urine flow increased to 2.8 +/- 0.7 ml/min and sodium excretion to 34 +/- 17 micromol/min. PRA decreased with control volume expansion but not during L-NAME. Urinary endothelin levels were elevated by L-NAME, decreased with volume expansion in all series, but excretion rate remained constant. Infusion of L-arginine partially reversed these effects of L-NAME. The results demonstrate that NO synthase inhibition increases blood pressure and blunts the renal responses to water and saline loading.
Peterson
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Department of Medical Physiology, Texas A&M University System Health Science Center, Reynolds Medical Building, College Station, TX 77843-1114, USA. tup@tamu.edu
Emmeluth
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D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D014556:Urine / Q000737:chemistry; D014882:Water-Electrolyte Balance
D004791:Enzyme Inhibitors; D001120:Arginine; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester