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 hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report.


METHODS
Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside.


RESULTS
Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5 +/- 0.5 vs. 8.9 +/- 2.6 mmHg2, 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 blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation.


CONCLUSIONS
Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.
Lambert
E
E
Laboratoire de Pharmacologie, CNRS UMR 8604, Faculté de Médecine Necker, Paris, France. elisabeth@baker.edu.au
Lambert
G
G
Fassot
C
C
Friberg
P
P
Elghozi
J L
JL
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000077300:Bosentan; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
D000959:Antihypertensive Agents; D016232:Endothelins; D020030:Nitric Oxide Donors; D013449:Sulfonamides; D009599:Nitroprusside; D009569:Nitric Oxide; D000077300:Bosentan