Brain nitric oxide synthase activity in normal, hypertensive, and stroke-prone rats.
OBJECTIVE
Nitric oxide-mediated cerebral vasodilation is altered in spontaneously hypertensive stroke-prone rats. Stroke predisposition in this strain could be related to a genetic defect of brain nitric oxide synthase, the enzyme responsible for nitric oxide production. We tested the hypothesis that brain nitric oxide synthase activity is altered in spontaneously hypertensive stroke-prone rats compared with spontaneously hypertensive or Wistar-Kyoto rats.


METHODS
A colony of spontaneously hypertensive stroke-prone rats was bred, in which the rate of neurological events under salt load was assessed. In a separate cohort of animals brain nitric oxide synthase activity was measured in spontaneously hypertensive stroke-prone rats (n = 6) and in spontaneously hypertensive (n = 6) and genetically related Wistar-Kyoto rats (n = 6). Calcium dependency of nitric oxide synthase was also assessed in cortical brain samples from the three rat strains to determine if altered calcium-dependent activation of nitric oxide synthase was present.


RESULTS
Brain nitric oxide synthase activity was highest in the cerebellum (eg, spontaneously hypertensive stroke-prone rats: cerebral cortex, 10.6 +/- 0.9; cerebellum, 50.1 +/- 12.0; brain stem, 14.7 +/- 10.3 pmol/mg protein per minute); however, there was no difference among the three rat strains in any region (eg, cerebral cortex: spontaneously hypertensive stroke-prone, 10.6 +/- 0.9; spontaneously hypertensive, 10.8 +/- 0.5; Wistar-Kyoto, 10.9 +/- 0.7 pmol/mg protein per minute) or at any calcium concentration tested.


CONCLUSIONS
A genetic defect of brain nitric oxide synthase is unlikely to be the cause of stroke predisposition in spontaneously hypertensive stroke-prone rats.
Clavier
N
N
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.
Tobin
J R
JR
Kirsch
J R
JR
Izuta
M
M
Traystman
R J
RJ
D000594:Amino Acid Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001933:Brain Stem / Q000201:enzymology; D002531:Cerebellum / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology; D002561:Cerebrovascular Disorders / Q000201:enzymology*; D005260:Female; D008297:Male; D019001:Nitric Oxide Synthase; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D013045:Species Specificity
D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases