PULSATILE STRETCH IN CORONARY-ARTERIES ELICITS RELEASE OF ENDOTHELIUM-DERIVED HYPERPOLARIZING FACTOR - A MODULATOR OF ARTERIAL COMPLIANCE

To date, the release of the endothelium-derived hyperpolarizing factor (EDHF) has been demonstrated only in response to receptor-dependent C a2+-elevating agonists. Since endothelial cells in situ are continuous ly subjected to rhythmic distension, we investigated the effect of rhy thmic stretch on the release of EDHF from isolated porcine coronary ar teries. In the combined presence of diclofenac and N-G-nitro-L-arginin e (L-NNA), sinusoidal pressure oscillations (from 40 to 50 mm Hg, 4 mi nutes, 1.5 Hz) led to simultaneous oscillations in the external diamet er of coronary artery segments, the amplitude of which were decreased by iberiotoxin and apamin and also by endothelial denudation, In order to directly demonstrate the release of EDHF, the intraluminal solutio n from endothelium-intact coronary segments exposed to pulsatile stret ch was applied to detector rat aortic smooth muscle cells, the membran e potential of which was continuously measured using the patch-clamp t echnique. The hyperpolarization of detector cells induced by the intra luminal solution was proportional to the amplitude of the pressure osc illations applied to the donor artery and was attenuated by either pre incubation of donor arteries with 17-octadecynoic acid or application of either tetrabutylammonium or iberiotoxin to detector cells. In cont rast to the bradykinin-induced release of EDHF, the EDHF synthesized i n response to pulsatile stretch did not exhibit any tachyphylaxis. The se findings demonstrate for the first time that the synthesis of EDHF in coronary arteries can be mechanically stimulated by rhythmic vessel wall distension and suggest that the continuous release of EDHF may c ontribute to the adjustment of an adequate vascular compliance and to the control of coronary blood flow.