Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may contribute to ischemia, but little is known about the contribution of intracerebral arterioles. In this study, the authors tested the hypothesis that SAH inhibits the vascular reactivity of intracerebral arterioles and documented the time course of this dysfunction.
Subarachnoid hemorrhage was induced using an endovascular filament model in halothane-anesthetized male Sprague-Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14 days postinsult, cannulated using a micropipette system that allowed luminal perfusion and control of luminal pressure, and evaluated for reactivity to vasodilator agents.
Spontaneous tone developed in all pressurized (60 mm Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar results in the sham and SAH groups. Subarachnoid hemorrhage did not affect dilation responses to acidic pH (6.8) but led to a persistent impairment of endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as well as a transient attenuation (p < 0.05) of vascular smooth muscle–dependent dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than adenosine- and 8-Br-cGMP–induced responses (up to 7 days postinsult compared with 2 days). All smooth muscle–dependent responses returned to sham levels by 14 days after SAH.
Subarachnoid hemorrhage led to a persistent impairment of endothelium-dependent dilation and a transient attenuation of vascular smooth muscle–dependent dilation responses to adenosine. Impairment of NOmediated dilation occurred when the response to cGMP was intact, suggesting a change in cGMP levels rather than an alteration in intracellular mechanisms downstream from cGMP.
Abbreviations used in this paper: ATP = adenosine triphosphate; cGMP = cyclic guanosine monophosphate; EDHF = endotheliumderived hyperpolarizing factor; ICA = internal carotid artery; MABP = mean arterial blood pressure; MOPS = 3-(N-morpholino)-propanesulfonic acid; SAH = subarachnoid hemorrhage; SE = standard error; sGC = soluble guanylate cyclase; SNP = sodium nitroprusside.
BendelOPrunellGStenqvistAMathiesenTHolminSSvendgaardNA: Experimental subarachnoid hemorrhage induces changes in the levels of hippocampal NMDA receptor subunit mRNA. Brain Res Mol Brain Res137:119–1252005
MacDonaldRLKakariekaAMayerSPasqualinARuefenachtDSchmiedekP: Prevention of cerebral vasospasm after aneurysmal subarachnoid hemorrhage with clazosentan, an endothelin receptor antagonist. 9th International Conference on Cerebral Vasospasm. June 27–30, 2006, Istanbul Turkey, The Marmara Hotel. Abstract Book2006. (Abstract OP5–3)
YouJJohnsonTDMarrelliSPMombouliJVBryanRMJr: P2u receptor-mediated release of endothelium-derived relaxing factor/nitric oxide and endothelium-derived hyperpolarizing factor from cerebrovascular endothelium in rats. Stroke30:1125–11331999