ABSTRACT
Endothel ium-dependent vasodi la ta t ion occurs i n response to a variety o f s t imul i , a l l o f wh ich activate endothelial cells to release vasoactive substances such as N O and endothelium-dependent hyperpolar izat ion. F o r instance, shear stress and pulsatile changes i n pressure (Popp et al, 1998) are two physiological ly relevant s t imul i for endothelium-dependent vasodilatat ion. A l s o , b r a d y k i n i n wh ich can be generated in vitro and in vivo by cleavage o f endothel ia l-bound k in inogen (van Iwaarden et al, 1988; H a s a n et al, 1995) by plasma ka l l ik r i en ( N i s h i k a w a et al, 1992), acts on B 2 k i n i n receptors to cause endothelium-dependent relaxation. Platelet aggregation is another physiologica l stimulus for endothelium-dependent relaxat ion (Cohen et al, 1983). However , whilst shear stress, pulsatile changes i n pressure and kininogenderived b r adyk in in most l ike ly activate the entire endothelial cell layer wi th in an arterial segment to release endothelium-derived relaxing factors ( E D R F s ) , adenosine diphosphate ( A D P ) and 5-hydroxytryptamine released by aggregating platelets at sites o f vascular damage are l ikely to only act as loca l activators. This raises the question whether or not loca l endothelial cell act ivat ion by platelet aggregation and the
76 Stavros Selemidis and Thomas M. Cocks
subsequent release o f E D R F s at this act ivat ion site, can be a sufficient stimulus for di la ta t ion o f the entire arterial annulus. A n affirmative answer to this important question cou ld be given i f the activated endothel ium was able to send an electrical signal to loca l under ly ing smooth muscle cells wh ich cou ld then travel a round the circumference o f the vessel v i a electrotonic coupl ing . Therefore, the a i m o f the present study was to determine whether local ly released E D R F s i n response to b radyk in in , A D P and 5-hydroxytryptamine evoke circumferental spread o f hyperpolar iza t ion to endothel ium-denuded regions o f the artery to relax the entire vessel.
