Mechanisms responsible for forskolin-induced relaxation of rat tail artery.

The goal of the present study was to determine the physiologically relevant mechanisms for forskolin-induced relaxation of intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and then relaxed the tissue with the addition of forskolin, a specific activator of adenylyl cyclase. We measured membrane potential with the use of microelectrodes, estimated intracellular Ca2+ concentration ([Ca2+]i) with the use of fura 2, and measured isometric force with a strain-gauge transducer. We found that 0.3 to 1.0 micromol/L forskolin relaxed 0.3 to 1.0 micromol/L phenylephrine-stimulated rat tail artery by decreasing the [Ca2+]i sensitivity of force as well as through repolarization. There was no evidence for forskolin-induced inhibition of Ca2+ influx beyond that associated with repolarization. There also was no evidence for forskolin-induced enhancement of Ca2+ efflux or sequestration. Inhibition of ATP-activated K+ channels with 10 micromol/L glibenclamide, Ca2+-activated K+ channels with 50 nmol/L iberiotoxin, Ca2+-activated K+ channels with 3 or 10 mmol/L tetraethylammonium ion, inwardly rectified K+ channels with 20 micromol/L Ba2+, and voltage-activated K+ channels with 0.5 mmol/L 4-aminopyridine did not significantly attenuate forskolin-induced reductions in [Ca2+]i or force. Forskolin-induced repolarization was not altered by 10 micromol/L glibenclamide or 0.5 mmol/L 4-aminopyridine. These data suggest that these K+ channels were not individually involved in forskolin-induced relaxation and that other channels and/or multiple channels are involved in forskolin-induced repolarization of intact rat tail artery. Our data also suggest that forskolin-induced relaxation of intact rat tail artery occurred primarily through repolarization and reductions in the [Ca2+]i sensitivity of force.