Increased sensitivity of cat cerebral arteries to serotonin upon elevation of transmural pressure

Segments of middle cerebral artery (MCA) were isolated from cat brains and cannulated allowing manipulation of transmural pressure (TP). These cannulated vessel segments were mounted in a specially fabricated myograph allowing measurement of internal diameter with the aid of a high resolution binocular microscope and a video imaging system. Internal diameter was then measured as a function of topically applied serotonin at 3 different levels of TP: 60, 100, and 140 mmHg. As TP was elevated from 60 to 140 mmHg the sensitivity to serotonin increased from an ED50 value of 1.3 x 10(-8) to 3.5 x 10(-10) M. We have yet to explore the mechanisms involved in the "pressure-mediated" increase in cerebrovascular sensitivity to serotonin; however, it may be related to the muscle membrane depolarization we have observed previously in response to elevations in TP. Such findings may account for the discrepancies in dose ranges for serotonin thought to be active in vivo vs. the higher concentrations needed to elicit responses in isolated vessels.