Contribution of Nitric Oxide Synthase [NOS] Activity in Blood-Brain Barrier Disruption and Edema after Acute Ischemia/ Reperfusion in Aortic Coarctation-Induced Hypertensive Rats

ABSTRACT

Nitric oxide synthase [NOS] activity is increased during hypertension and cerebral ischemia. NOS inactivation reduces stroke-induced cerebral injuries, but little is known about its role in blood-brain barrier [BBB] disruption and cerebral edema formation during stroke in acute hypertension. Here, we investigated the role of NOS inhibition in progression of edema formation and BBB disruptions provoked by ischemia/reperfusion injuries in acute hypertensive rats. Rats were made acutely hypertensive by aortic coarctation. After 7 days, the rats were randomly selected for the recording of carotid artery pressure, or regional cerebral blood flow [rCBF] using laser Doppler. Ishcemia induced by 60-min middle cerebral artery occlusion [MCAO], followed by 12-h reperfusion. A single i.p. dose of L-NAME [1 mg/kg] was injected before MCAO. After evaluation of neurological disabilities, rats were slaughtered under deep anesthesia to assess cerebral infarction volume, edema, or BBB disruption. A 75-85% reduction in rCBF was occurred during MCAO which returned to pre-occluded levels during reperfusion. Profound neurological disabilities were evidenced after MCAO alongside with severe cerebral infarctions [628 +/- 98 mm[3]], considerable edema [4.05 +/- 0.52%] and extensive BBB disruptions [Evans blue extravasation, 8.46 +/- 2.03 [microg/g]. L-NAME drastically improved neurological disabilities, diminished cerebral infarction [264 +/- 46 mm[3]], reduced edema [1.49 +/- 0.47%] and BBB disruption [2.93 +/- 0.66 microg/g]. The harmful actions of NOS activity on cerebral microvascular integrity are intensified by ischemia/reperfusion injuries during acute hypertension. NOS inactivation by L-NAME preserved this integrity and diminished cerebral edema