Apoptosis and glomerular injury after prolonged nitric oxide synthase inhibition in spontaneously hypertensive rats.
This study was designed to investigate the relationship between apoptosis and glomerular injury in spontaneously hypertensive rats (SHR) with hypertensive disease that was exacerbated by inhibition of NO synthesis. Development of glomerular cell apoptosis was evaluated by assessment of renal hemodynamics, glomerular morphometric changes, and participation of the renin-angiotensin system. Three groups of 20-week-old SHR were investigated: control male SHR and 2 similar groups given 2 doses of N(G)-nitro-L-arginine methyl ester (L-NAME, 50 or 80 mg/L, respectively) for 3 weeks. Mean arterial pressure and renal vascular resistance increased, whereas effective renal plasma flow and glomerular filtration rate were diminished by L-NAME. The small artery wall/lumen ratio increased as the glomerular-tuft area diminished. Renal cortical tissue levels of angiotensin II increased in response to the L-NAME, thereby inducing afferent arteriolar injury. Apoptosis and proliferative index (PCNA) of nonsclerotic glomeruli were induced by the low-dose L-NAME as the glomerular cell number decreased. In contrast, the PCNA index was downregulated with the high-dose L-NAME. These results indicate that angiotensin II activation, induced by L-NAME, was related to glomerular cell deletion and apoptosis together with the pathophysiological changes of severe nephrosclerosis and impaired renal dynamics.
Ono
H
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Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, LA 70121, USA.
Ono
Y
Y
Takanohashi
A
A
Matsuoka
H
H
Frohlich
E D
ED
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000648:ultrastructure; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow
D000804:Angiotensin II; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester