L-arginine-induced regional cerebral blood flow increase is abolished after transient focal cerebral ischemia in the rat.
We investigated the L-arginine-induced, regional cerebral blood flow (rCBF) enhancement after different durations of transient focal cerebral ischemia in the rat to determine if L-arginine increases rCBF after transient focal cerebral ischemia. Focal ischemia (5 minutes and 20 minutes) followed by 90 minutes of reperfusion was induced in a normotensive rat suture-model. Regional cerebral blood flow in both hemispheres was measured by laser-Doppler-flowmetry. Reactivity of rCBF to L-arginine (300 mg/kg) was measured 45 minutes after reperfusion, and hypercapnia 90 minutes after reperfusion. The effect of D-arginine and pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NA) (10 mg/kg) was examined in additional groups. Hypercapnia and L-arginine increased rCBF in sham operated controls and on the nonischemic hemispheres. D-arginine did not. Twenty-minute long ischemia significantly reduced the response to L-arginine (control side: 115 +/- 5.9%; ischemic side: 107 +/- 6.1%, n = 7) and hypercapnia, 5 minutes of ischemia did not. N(omega)-nitro-L-arginine pretreatment partly restored the L-arginine-induced rCBF increase. Thus, rCBF increase caused by L-arginine in the reperfusion period was unaffected by 5 minutes of ischemia, but reduced by 20 minutes of ischemia. The restoration after pretreatment with L-NA may be caused by attenuated production of cytotoxic substances, e.g., NO and related compounds.
Sporer
B
B
Ludwig-Maximilians-Universität München, Neurologische Klinik, Germany.
Martens
K H
KH
Koedel
U
U
Haberl
R L
RL
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D004791:Enzyme Inhibitors; D002245:Carbon Dioxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester