Moderate hypothermia attenuates the endothelium-dependent pial arteriole dilatation but not the endothelium-independent response in rats

Hypothermia is a tool providing cerebral protection in the management for traumatic brain injury and cardiovascular bypass surgery. However, alteration in vasodilatory function of cerebral pial arteriole under hypothermic conditions is not fully understood. We examined the cerebrovascular response to topically administered vasodilators under normo- and hypothermic conditions. All animals were anesthetized by urethane/alpha-chloralose (i.p.), tracheostomized, and ventilated, and the physiological parameters (rectal temperature, end-tidal (ET) CO2, blood pressure, pulse rate, and arterial blood gas analysis) were monitored. Using the closed cranial window method with video microscopy, pial arteriolar caliber change was monitored before and after superfusion of the endothelium-dependent vasodilator, acetylcholine (ACh), the endothelium-independent NO donor, sodium nitroprusside (SNP), and the cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibitor, cilostazol. Experiments were carried out first under normothermia, then the hypothermic condition (rectal temperature 30degreesC with alpha-stat management) was introduced and the protocol was repeated. Under normothermia, topical application of ACh caused a dose-dependent increase in arteriolar diameter that was significantly attenuated after hypothermia induction. Sodium nitroprusside and cilostazol stimulated vasodilation during normothermia to a maximum of 30% +/- 12% and 17% +/- 9%, respectively. Under hypothermia these values were 43% +/- 12% and 26% +/- 15%, respectively. Hypothermia did not alter the vasodilation in response to SNP and cilostazol. The specific loss of ACh-induced vasodilation suggests endothelial cell dysfunction. The cAMP phosphodiesterase inhibitor cilostazol can dilate cerebral arterioles both under normo- and hypothermic conditions.