Impairment of intracerebral arteriole dilation responses after subarachnoid hemorrhage

Laboratory investigation

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Object

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.

Methods

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.

Results

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.

Conclusions

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.

Article Information

Address correspondence to: Gavin W. Britz, M.D., M.P.H., Duke University Medical Center, Box 3807, Durham, North Carolina 27710. email: gavin.britz@duke.edu.

Please include this information when citing this paper: published online May 1, 2009; DOI: 10.3171/2009.3.JNS096.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Bar graph showing dilation response to adenosine (adventitial application) in intracerebral arterioles isolated from rats in the sham and SAH groups. Values are means ±SEs. *p < 0.05 compared with the sham group.

  • View in gallery

    Bar graph showing dilation response to SNP (adventitial application) in intracerebral arterioles isolated from rats in the sham and SAH groups. Values are means ± SEs. *p < 0.01 compared with the sham group.

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    Bar graph showing dilation response to ATP (luminal application) in intracerebral arterioles isolated from rats in the sham and SAH groups. Values are means ±SEs. *p < 0.01 compared with the sham group.

  • View in gallery

    Bar graph showing dilation response to 8-Br-cGMP (adventitial application) in intracerebral arterioles isolated from rats in the sham and SAH groups. Values are means ±SEs. *p < 0.05 compared with the sham group.

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