Effects of Indomethacin on Myogenic Contractile Activation and Responses to Changes in O2 and CO2 in Isolated Feline Cerebral Arteries

Abstract

Summary: We used an isolated, pressurized, and perfused feline middle cerebral artery preparation to measure how changes in intraluminal pressure and alterations in 0₂ and C0₂ affect vessel diameter and myogenic contractile activation before and after treatment with indomethacin (IND). Vessel diameters were measured over the pressure range 60-140 mm Hg. The arteries were then exposed to low 0₂ (50 torr) and/or high C0₂ (65 torr) and diameters remeasured over the same range. Under control conditions, the arteries exhibited myogenic contractile activation. Exposure to low 0₂, high C0₂, or a mixture of low 0₂/high C0₂, increased vessel diameter but did not change the vessels' myogenic contractile responsiveness to changes in pressure. Arteries exposed to IND decreased in diameter but retained myogenic contractile activity. In the presence of IND, vessels dilated to both low 0₂ and a mixture of low 0₂/high C0₂, but did not dilate to high C0₂ alone. Under all conditions, vessels retained myogenic contractile activity. Results obtained under control conditions and low 0₂ confirm those of others using similar systems. Myogenic contractile activity in the presence of high C0₂ or a mixture of low 0₂/ high C0₂ has not been previously reported. The dilation to low 0₂ but not to high C0₂ in the presence of IND suggests that this drug's effects in cerebral arteries are not limited solely to inhibition of prostaglandin synthesis.