The role of constitutive and inducible nitric oxide synthase in the human brain after subarachnoid hemorrhage

Aim. Results of prior experimental studies show that nitric oxide (NO) plays an important role in the pathogenesis of vasospasm. In the present study, the expression of endothelial NO synthase (eNOS), neuronal NO synthase (nNOS) and of inducible NO synthase (iNOS) in the human brain after subarachnoid haemorrhage were studied. Methods. Twenty-three samples of gyrus rectus or temporal operculum that were obtained during a surgical approach to anterior circulation aneurysms were used for this study. Seven samples were obtained during surgery from patients who underwent operation for unruptured aneurysms (control group). eNOS-mRNA, nNOS-mRNA and iNOS-mRNA were extracted and amplified by RT-PCR. Patients were subdivided for intergroup comparison by: age < 60 / > 60 years; source of sample; clinical grading; extent of subarachnoid clot; presence of intracerebral/intraventricular hematoma; surgical timing; vasospasm; outcome. Results. There was a significant increase in the expression of eNOS between SAH and control groups (P=0.046); eNOS hyperexpression was higher in the patients in poor clinical conditions (P=0.002) and lasted until the late phase of haemorrhage. nNOS overall expression was unchanged but hyperexpression was observed in the patients in poor clinical conditions (P=0.008). There was a significant hyperexpression of iNOS in SAH group (P=0.026), and in patients with vasospasm (P=0.0024); the expression was significantly reduced in the late phase of haemorrhage (P=0.0038). Conclusion. The acute decrease of NO after SAH is not determined by reduced constitutive NOS expression and iNOS induction is a consequence of SAH and plays a major role in the pathogenesis of vasospasm.