Abstract
August Krogh first reported that the local application of vasodilators could stimulate extensive vasodilatation which spreads rapidly to distant sites. Conducted responses of this type are referred to as spreading dilatation, a response which cannot be explained simply on the basis of diffusion of the locally applied dilator agent. The present study was designed to test the hypothesis that local stimulation of hyperpolarization can be conducted longitudinally over significant distances to spread dilatation in small mesenteric arteries. A segment of mouse mesenteric artery was cannulated at each end with a glass pipette and then pressurized. In the presence of the NO synthase inhibitor, L-NAME, focal application of the PAR2 agonist, SLIGRL induced dilatation at the site of application. This local dilatation was associated with simultaneous dilatation along the entire artery segment. Measurement of smooth muscle membrane potential revealed local hyperpolarization to SLIGRL which was also observed at distant sites. In contrast, focal application of forskolin did not induced any hyperpolarization, and although it evoked local dilatation, this was not associated with any coordinated dilatation along the isolated mesenteric artery. These results indicate that spreading dilatation responses in mesenteric resistance arteries are only evoked with vasodilators which hyperpolarize the artery. [J Physiol Sci. 2006;56 Suppl:S133]
