ABSTRACT
N i t r i c oxide can modulate coronary arterial tone in vivo as it is the mediator o f shear stress signaling ( R u b a n y i et al, 1986; O h n o et al, 1993), perfusion pulsat i l i ty (Recchia et al, 1996; Pagl iaro et al, 1999) and endothelium-dependent relaxations to agonists such as acetylcholine and b radyk in in . In a variety o f arteries, however, a component o f endothelium-dependent dilatat ions are resistant to inh ib i t ion o f ni tr ic oxide synthase and cyclooxygenase. The mechanism under lying this pathway is relaxat ion o f vascular smooth cells mediated by an endothelium-derived hyperpola r iz ing factor ( E D H F ) (Qui l ley et al., 1997) whose nature remains controversial
Role of charybdotoxin!'apamin sensitive K^a channels 305 (Cohen et al., 1997; Edwards et al., 1998; Fissl thaler et al., 1999). A c o m m o n footprint o f E D H F - m e d i a t e d relaxat ion is the act ivat ion o f calcium-dependent potassium ( K ¿ a ) channels inhibi table by charybdotox in plus apamin ( F é l é t o u and Vanhout te , 1999). These channels may also be activated by ni tr ic oxide and c y c l i c G M P (Rober tson et al., 1993; B o l o t i n a et al., 1994) suggesting a role o f K j a channels conductance to ni tr ic oxide (Archer et al., 1994) and shear stress signaling as wel l (Takamura et al, 1999).
