L-arginine reverses severe nephrosclerosis in aged spontaneously hypertensive rats.
OBJECTIVE
Acute and prolonged effects of L-arginine on systemic and renal hemodynamics and on renal pathological changes were examined in 85-week-old spontaneously hypertensive rats (SHR).


RESULTS
After 3 weeks of L-arginine administration (n = 9; 2 g/l in drinking water), mean arterial pressure remained unchanged, although the cardiac index increased (187 +/- 26 versus 263 +/- 15 ml/min per kg; P < 0.05) and total peripheral resistance decreased (1.15 +/- 0.18 versus 0.67 +/- 0.06 AU; P < 0.05); the glomerular filtration rate increased (0.41 +/- 0.07 versus 0.79 +/- 0.07 ml/min; P < 0.01). Control untreated, aged SHR (n = 10) demonstrated severe nephrosclerosis histologically, but those treated with L-arginine demonstrated a markedly reduced glomerular injury score (164 +/- 22 versus 83 +/- 9; P < 0.005), and their urinary protein excretion (39 +/- 5 versus 19 +/- 5 mg/100 g body weight per day; P < 0.05) and serum creatinine concentration (1.4 +/- 0.1 versus 0.9 +/- 0.1 mg/dl; P < 0.05) diminished. Intravenous L-arginine (300 mg/kg body weight) given to untreated SHR reduced mean arterial pressure, increased the cardiac index (+98 versus +1%; P < 0.05) and decreased total peripheral resistance (+56 versus +13%, P < 0.005); however, these variables remained unchanged after 3 weeks of L-arginine treatment.


CONCLUSIONS
Three weeks of treatment with L-arginine improved systemic hemodynamics, renal function and renal histologic changes in aged SHR with naturally occurring nephrosclerosis. These data provide an important insight into the pathophysiology of nephrosclerosis in hypertension and with aging, which is seen clinically.
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Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, Louisiana, USA.
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Frohlich
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D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009400:Nephrosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size; D051381:Rats; D011918:Rats, Inbred SHR; D012720:Severity of Illness Index; D014655:Vascular Resistance / Q000187:drug effects
D001120:Arginine