DIVERGENT MECHANISMS OF ATP-SENSITIVE K-INDUCED VASODILATION IN RENALAFFERENT AND EFFERENT ARTERIOLES - EVIDENCE OF L-TYPE CA2+ CHANNEL-DEPENDENT AND CHANNEL-INDEPENDENT ACTIONS OF PINACIDIL( CHANNEL)

K+ channel openers (PCOs), such as pinacidil, elicit vasodilation prim arily by hyperpolarization-induced inhibition of L-type Ca2+ channel a ctivation. The physiological role of other mechanisms suggested to con tribute to PCO-induced vasodilation is not well established. In the re nal microcirculation, L-type Ca2+ channels play a prominent role in va soconstriction of the afferent arteriole (AA) but are absent or physio logically silent in the efferent arteriole (EA). Thus, L-type Ca2+ cha nnel-dependent and -independent mechanisms can readily be distinguishe d in this model. In the present study, we found that pinacidil potentl y inhibited Bay K 8644-induced AA vasoconstriction, Pinacidil also pre ferentially inhibited angiotensin II-induced AA vasoconstriction (appr oximately ninefold greater potency than EA). These results are consist ent with an AA effect of pinacidil on L-type Ca2+ channel activation. Unexpectedly, 10 mu mol/L pinacidil inhibited AA and EA responses to s imilar extents (84+/-10% and 71+/-9%, respectively). In both AAs and E As, glibenclamide restored normal reactivity, indicating an involvemen t of the ATP-sensitive K+ channels. In the EA, however, pretreatment w ith diltiazem did not alter the effects of pinacidil. Nevertheless, 45 mmol/L KCL reversed the EA actions of pinacidil, indicating an essent ial requirement for a normal K+ gradient. These findings suggest that the EA actions of pinacidil involve alterations in membrane potential but not changes in L-type Ca2+ channel activity, Overall, our findings do support the premise that L-type Ca2+ channel modulation is involve d in PCO-induced vasodilation in the renal microcirculation. The EA ac tions of pinacidil, however, suggest important additional vasodilatory mechanisms that also involve ATP-sensitive Ke channel-induced hyperpo larization but are independent of L-type Ca2+ channel modulation.