Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function.
We conducted longitudinal measurements of blood pressure and renal function in the conscious, chronically catheterized rat before and during acute nitric oxide synthase inhibition (N-nitro-L-arginine methylester [L-NAME], 37 micromol/kg IV) and then chronic administration of oral L-NAME (approximately 37 micromol/kg per 24 hours). These studies specifically investigate the impact on plasma and renal renin as well as volume status during the evolution of this hypertension in rats not subjected to acute experimental stress. Blood pressure progressively increased with chronic administration of L-NAME and reached values greatly above those seen with acute administration of L-NAME. There were parallel increases in renal vascular resistance and development of proteinuria, and glomerular filtration rate began to decline at day 21, coincident with the appearance of renal damage. Twenty-four-hour urinary nitrite and nitrate excretion remained depressed, reflecting reduced nitric oxide synthesis. The plasma renin activity was variable and only increased transiently at 21 days, thus the angiotensin II dependence of this hypertension is not caused by stimulated plasma renin activity. Despite severe hypertension, sodium intake and excretion were unchanged over the 21 days of L-NAME administration. Plasma volume was significantly reduced at days 2 and 12 of L-NAME administration; thus the prolonged plasma volume contraction must result from the acute natriuretic response to the initial acute L-NAME administration.
Qiu
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Department of Physiology, West Virginia University, Morgantown 26506-9229, USA.
Muchant
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Beierwaltes
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Racusen
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Baylis
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D019001:Nitric Oxide Synthase; D012083:Renin; D019331:NG-Nitroarginine Methyl Ester