Temporal profiles of Ca2+/calmodulin-dependent and -independent nitric oxide synthase activity in the rat brain microvessels following cerebral ischemia.

The present study was aimed at determining chronological alterations of Ca2+/calmodulin (CaM)-dependent and -independent nitric oxide synthase (NOS) activities in brain microvessels (MV) isolated from the affected hemisphere following an occlusion of the middle cerebral artery (MCAo) in rats. It was shown that significant enhancements of Ca2+/CaM-independent NOS activity to 922% and 920% of control level were manifested at 4 h and 24 h, respectively, which returned to the control level at 48 h after MCAo. Regarding Ca2+/CaM-dependent NOS, on the other hand, it was shown that the activity was invariably increased to 374% and 743% of control level at 48 h and 1 week following MCAo, respectively. Thus, the present study provided the first evidence that two distinct types of NOS activities were increased with different temporal patterns after MCAo. These heterogeneous alterations of NOS activities may be of critical importance for the induction of brain damage following cerebral ischemia.