Changes in Endothelial Nitric Oxide Synthase mRNA during Vasospasm after Subarachnoid Hemorrhage in Monkeys

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Abstract
We attempt to determine whether changes in messenger ribonucleic acid (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes that mediate endothelium-dependent vasodilation in cerebral arteries, occur after subarachnoid hemorrhage (SAH) in monkeys. Baseline cerebral angiograms were obtained, and right-sided SAH was induced by microsurgically placing autologous blood clot against the right anterior circle of Willis in seven monkeys. Seven days later, angiographic studies were repeated and the animals were killed. Right (vasospastic) and left (control) middle cerebral arteries and underlying cortex were removed. The competitive reverse transcriptase polymerase chain reaction was used to quantify mRNA for soluble guanylate cyclase and two isoforms of constitutive NOS in these tissues. Comparison of angiograms at baseline and after 7 days showed a 41 ± 7% (mean ± standard error of the mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral artery. After the animals were killed, comparison of right and left middle cerebral arteries showed a 56 ± 11 % decrease (P < 0.005, paired t test) in endothelial NOS mRNA. There was a 142 ± 39% (P < 0.05) increase in right cortex endothelial NOS mRNA compared to the left cortex. There were no significant differences between right and left sides in mRNAs for soluble guanylate cyclase or brain NOS. Decreased endothelial NOS mRNA in cerebral arteries 7 days after SAH may be caused by endothelial cell damage and could contribute to vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a compensatory vasodilator mechanism of the brain against the cerebral ischemia associated with vasospasm and SAH.