L-arginine ameliorates recirculation and metabolic derangement in brain ischemia in hypertensive rats.
The effects of L-arginine (a precursor of nitric oxide, NO) on cerebral blood flow (CBF), cerebrovascular resistance (CVR) and metabolites in the ischemic brain were examined in spontaneously hypertensive rats with bilateral carotid artery occlusion for 30 min followed by 60 min-recirculation. The administration of L-arginine (300 mg/kg, i.v.) increased the CBF by an average of 11 ml x 100 g-1 x min-1 (P < 0.05 vs. at rest), and N(omega)-nitro-L-arginine (L-NNA, an inhibitor of NO synthase, 5 mg/kg, i.v.) reduced the CBF by 5-6 ml x 100 g-1.min-1 with increase in the mean arterial pressure by 26 mmHg. During ischemia the CBF significantly decreased to below 8% of the resting values in all rats. The largest blood flow in postischemic hyperemia was 171 +/- 9% of the resting CBF in the rats with L-arginine (P < 0.05 vs. L-NNA and saline), followed by 126 +/- 5 with saline and 109 +/- 3 with L-NNA. The CVR at 60 min of recirculation was 3.291 +/- 0.144 mmHg . ml-1. 100 g-1 .min-1 in the rats with saline, remained low level of 2.711 +/- 0.124 with L-arginine (P < 0.01 vs. L-NNA and P < 0.05 vs. saline) and in contrast, significantly increased to 5.732 +/- 0.184 with L-NNA (P < 0.01 vs. L-arginine and saline, respectively). Tissue lactate with saline increased 2.3-fold at 60 min of recirculation, whereas the increase was inhibited to 1.4-fold after L-arginine treatment (P < 0.01 vs. L-NNA) and in contrast, significantly increased 5.7-fold with L-NNA. The ATP and glucose levels were better preserved in the rats with L-arginine than in those with L-NNA or saline. These findings support that the enhanced postischemic hyperemia is beneficial to the ischemic brain and the administration of L-arginine may be potentially useful for the treatment of acute stroke.
Sadoshima
S
S
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Nagao
T
T
Okada
Y
Y
Fujii
K
K
Ibayashi
S
S
Fujishima
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects*
D001120:Arginine