Effects of inhibition of nitric oxide synthase on blood-brain barrier transport in focal cerebral ischemia.
This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ischemia.
Chi
O Z
OZ
Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick 08903-0019.
Wei
H M
HM
Sinha
A K
AK
Weiss
H R
HR
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000502:physiology*; D002545:Brain Ischemia / Q000201:enzymology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D051381:Rats
D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester