Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity

Objective: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemor rhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the p resent report. Methods: Subarachnoid hemorrhage was induced in conscious ra ts by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arte rial plasma catecholamines with the spectral analysis of blood pressure var iability in order to examine sympathetic nervous activation following subar achnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. R esults: Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequ ency components of blood pressure were markedly elevated following subarach noid hemorrhage (2.5+/-0.5 vs. 8.9+/-2.6 mmHg(2), P<0.01). parallel changes in plasma norepinephrine concentration were observed (1.0+/-0.2 vs. 2.4+/- 0.4 nmol/l, P<0.01). The subarachnoid injection of saline did not modify bl ood pressure variability or plasma norepinephrine concentrations. Pretreatm ent with either bosentan or sodium nitroprusside completely prevented the s ubarachnoid hemorrhage induced sympathoexcitation. Conclusions: Experimenta l subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation h as its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation. (C) 2000 Elsevier Science B,V. All rights reserved.