Acetylcholine- and flow-induced production and release of nitric oxide in arterial and venous endothelial cells. Fukaya, Yukio, and Toshio Ohhashi. The 1st Department of Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan
APStracts 2:0313H, 1995.
In order to study flow-mediated responses in a conduit vein, we investigated the physiological characteristics of endothelium -dependent acetylcholine (ACh)- and flow-induced relaxations using a conventional bioassay cascade. Cylindrical segments isolated from canine common carotid arteries and external jugular veins were perfused at a constant mean flow rate ranging from 1 to 8 ml/min. Endothelium-derived nitric oxide activity in perfusion effluent through the arterial and venous segments was measured by relaxation of endothelium-denuded arterial and arterial and/or venous rings precontracted by prostaglandin F2[alpha], respectively. Stimulation by a flow rate of 8 ml/min on the arterial and venous endothelial cells produced about 60 % and 20 % of the maximum relaxation in the arterial and venous rings, respectively. ACh (10-6 and 10-5 M) perfused through the arterial and venous segments with endothelium caused dose-related relaxations of the both bioassay rings. The ACh- and flow-induced relaxation were completely reduced by mechanical removal of the endothelial cells. Pretreatment with 5 x 10-5 M L -nitro-arginine methylester (L-NAME) produced a significant reduction of the ACh- and flow-induced vasodilation. Additional treatment with 10-4 M L-arginine significantly reversed the L-NAME-induced inhibition of ACh-induced relaxation, but had no effect on flow -induced relaxation. When the flow rate was increased from 2 to 4 ml/min, the same concentrations of ACh produced larger dose-related relaxations than those obtained at a flow rate of 2 ml/min. Pretreatment with 25 U/ml superoxide dismutase caused no significant effect on the flow-mediated potentiation of ACh-induced relaxation. These findings suggest that venous endothelial cells of canine large vein are able to produce and release of nitric oxide by the stimulation of increased flow or ACh with a significantly lesser extent compared with the artery, and that ACh-induced vasodilation is potentiated by an increase of shear stress up to about 4 dynes/cm2 loaded on the endothelial cells.

Received 22 November 1994; accepted in final form 12 July 1995.
APS Manuscript Number H1037-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.