Mechanism of action of vasoactive intestinal polypeptide on cerebral arterioles

The effect of vasoactive intestinal polypeptide (VIP) on cerebral arterioles was examined in anesthetized cats equipped with an acutely implanted cranial window for the observation of the pial microcirculation. Topical application of VIP on the surface of the brain in doses of 0.01-1.0 microgram/ml produced a dose-related vasodilation that was of equal magnitude in small (< 100 micrometer diam) and large (> 100 micrometer diam) pial arterioles. The maximum dilation averaged 20% of the control diameter. There were no associated changes in arterial blood pressure or in arterial CO2 tension. In additional experiments the vasodilator effect of VIP was completely inhibited by pretreatment with intravenous indomethacin or AHR-5850. These nonsteroidal anti-inflammatory drugs inhibit cyclooxygenase activity and thereby interfere with the synthesis of prostaglandins and related compounds. The vasodilator effect to topical histamine was unaffected by indomethacin and AHR-5850. The results show that VIP has a strong vasodilator effect on pial arterioles of the cat and suggest that this effect is mediated by prostaglandins.