title: Nitric oxide synthase inhibition in spontaneously hypertensive rats. Systemic, renal, and glomerular hemodynamics.
abstract: 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)
authors.affiliation: Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, LA 70121-2484, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Ono
authors.forename: E D
authors.initials: ED
authors.lastname: Frohlich
mesh_terms: 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*
chemical_list: D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester