Microcirculatory responses to exogenous endothelial cell-derived relaxing factor

Abstract

Endothelium-derived relaxing factor (EDRF) plays an important role in the vasodilatory responses of large blood vessels. However, such a role has yet to be conclusively shown for the microvasculature. In this study we tested the sensitivity of arterioles in the cheek pouch of pentobarbital-anesthetized hamsters to the EDRF-dependent agonists bradykinin and A23187, as well as to exogenous EDRF from cultured bovine aortic endothelial cells. The pouch superfusion fluid was arranged to first pass through a column containing endothelial cells and then on to the tissue. Bradykinin (10–30 nM) or A23187 (0.3 microM) was introduced either upstream or downstream to the endothelial cells, and the resultant responses were measured with video microscopy. Bradykinin and A23187 both caused a dose-dependent release of a microvessel dilator from cultured endothelial cells. We take this dilator to be EDRF based on the characteristics of the responses to the stimuli. Indomethacin (7.7 microM) was present in the superfusate to eliminate the production of cyclooxygenase products from the endothelial cells, and the magnitude of the response was diminished if the superfusate was first passed through a 3-min delay coil before arrival at the pouch. The arterioles dilated to the direct application of bradykinin in a dose-dependent fashion. They did not respond however to the direct application of A23187. These studies demonstrate that arteriolar smooth muscle is able to respond to exogenous EDRF and support the premise that EDRF may play an active role in the regulation of blood flow in the microcirculation.