Nitric oxide synthase inhibition in spontaneously hypertensive rats. Systemic, renal, and glomerular hemodynamics.
To investigate the prolonged effects of nitric oxide inhibition on systemic, renal, and glomerular hemodynamics, the effects of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on cardiac index, renal micropuncture results, urinary excretion, and histology were obtained in 20-week-old male spontaneously hypertensive rats (SHR) that were divided into two groups: untreated and L-NAME-treated (50 mg/L), each followed for 3 weeks. Cardiac index and effective renal plasma flow decreased (P < .01) in L-NAME-treated SHR, exhibiting a positive correlation (r = .816; P < .0001). Single-nephron plasma flow (123 +/- 8 versus 80 +/- 12 nL/min per gram; P < .01) and ultrafiltration coefficient (P < .05) were also reduced in L-NAME-treated SHR versus controls. Most notably, the L-NAME-treated SHR had increased afferent (4.4 +/- 0.3 versus 9.5 +/- 1.3 U; P < .01) and efferent (1.4 +/- 0.1 versus 2.7 +/- 0.3 U; P < .01) glomerular arteriolar resistances versus controls. These functional changes were associated with significantly altered afferent arteriolar (P < .001) and glomerular (P < .005) histological injury scores accompanied by marked proteinuria (P < .001). Because of the intense afferent glomerular artery constriction and lesser increase in efferent glomerular arteriolar resistance associated with reduced single-nephron plasma flow, glomerular capillary pressure did not increase in the L-NAME-treated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, LA 70121-2484, USA.
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Frohlich
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects*
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester