Exogenous L-arginine ameliorates angiotensin II-induced hypertension and renal damage in rats.
Experiments were performed to determine whether exogenous L-arginine could ameliorate angiotensin II-induced hypertension and renal damage. Rats were instrumented with chronic indwelling femoral venous and arterial catheters for infusions of drugs and measurement of conscious arterial pressure. Arterial blood pressure significantly increased from 124+/-1 to 199+/-4 mm Hg, after 9 days of continuous infusion of angiotensin II (20 ng/kg per minute; IV; n=6 to 9). In contrast, the increase in arterial pressure after 9 days of angiotensin II infusion was significantly blunted by 45% (P=0.0003) in rats coadministered L-arginine (300 microg/kg per minute; IV; n=7 to 9). The glomerular injury index was significantly greater in rats administered angiotensin II in comparison with rats administered saline vehicle (P<0.001). Coinfusion of L-arginine significantly increased plasma nitrate/nitrite concentrations (P<0.001) and completely prevented angiotensin II-induced glomerular damage (P<0.001). Angiotensin II infusion alone and combined angiotensin II plus L-arginine infusion significantly increased urinary albumin excretion. Albuminuria in rats administered angiotensin II plus L-arginine is likely to be because of increased intraglomerular pressure. Our experiments demonstrate that L-arginine can blunt angiotensin II-induced hypertension and associated renal damage. This latter observation is most exciting because it indicates that increasing NO bioavailability, in addition to lowering arterial pressure, can greatly reduce hypertension-induced renal damage.
Rajapakse
Niwanthi W
NW
Department of Physiology, Medical College of Wisconsin, Milwaukee, USA. niwanthi.rajapakse@med.monash.edu.au
De Miguel
Carmen
C
Das
Satarupa
S
Mattson
David L
DL
D000419:Albuminuria / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003243:Consciousness; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005919:Glomerular Filtration Rate; D006977:Hypertension, Renal / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D009573:Nitrites / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D009566:Nitrates; D009573:Nitrites; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D003404:Creatinine