BRAIN NITRIC-OXIDE SYNTHASE ACTIVITY IN NORMAL, HYPERTENSIVE, AND STROKE-PRONE RATS

Background and Purpose Nitric oxide-mediated cerebral vasodilation is altered in spontaneously hypertensive stroke-prone rats. Stroke predis position in this strain could be related to a genetic defect of brain nitric oxide synthase, the enzyme responsible for nitric oxide product ion. We tested the hypothesis that brain nitric oxide synthase activit y 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 th e rate of neurological events under salt load was assessed. In a separ ate cohort of animals brain nitric oxide synthase activity was measure d in spontaneously hypertensive stroke-prone rats (n=6) and in spontan eously 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 alte red calcium-dependent activation of nitric oxide synthase was present. Results Brain nitric oxide synthase activity was highest in the cereb ellum (eg, spontaneously hypertensive stroke-prone rats: cerebral cort ex, 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 thr ee rat strains in any region (eg, cerebral cortex: spontaneously hyper tensive 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 calc ium concentration tested. Conclusions A genetic defect of brain nitric oxide synthase is unlikely to be the cause of stroke predisposition i n spontaneously hypertensive stroke-prone rats.