Divergent mechanisms of ATP-sensitive K+ channel-induced vasodilation in renal afferent and efferent arterioles. Evidence of L-type Ca2+ channel-dependent and -independent actions of pinacidil.
K+ channel openers (PCOs), such as pinacidil, elicit vasodilation primarily by hyperpolarization-induced inhibition of L-type Ca2+ channel activation. The physiological role of other mechanisms suggested to contribute to PCO-induced vasodilation is not well established. In the renal microcirculation, L-type Ca2+ channels play a prominent role in vasoconstriction of the afferent arteriole (AA) but are absent or physiologically silent in the efferent arteriole (EA). Thus, L-type Ca2+ channel-dependent and -independent mechanisms can readily be distinguished in this model. In the present study, we found that pinacidil potently inhibited Bay K 8644-induced AA vasoconstriction. Pinacidil also preferentially inhibited angiotensin II-induced AA vasoconstriction (approximately ninefold greater potency than EA). These results are consistent with an AA effect of pinacidil on L-type Ca2+ channel activation. Unexpectedly, 10 mumol/L pinacidil inhibited AA and EA responses to similar extents (84 +/- 10% and 71 +/- 9%, respectively). In both AAs and EAs, glibenclamide restored normal reactivity, indicating an involvement of the ATP-sensitive K+ channels. In the EA, however, pretreatment with diltiazem did not alter the effects of pinacidil. Nevertheless, 45 mmol/L KCl reversed the EA actions of pinacidil, indicating an essential 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 involved in PCO-induced vasodilation in the renal microcirculation.(ABSTRACT TRUNCATED AT 250 WORDS)[1]References
- Divergent mechanisms of ATP-sensitive K+ channel-induced vasodilation in renal afferent and efferent arterioles. Evidence of L-type Ca2+ channel-dependent and -independent actions of pinacidil. Reslerova, M., Loutzenhiser, R. Circ. Res. (1995) [Pubmed]
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