Renal vasoconstriction elicited by a cocktail of potassium channel blockers

Abstract

Inhibition of K+ channels might mediate agonist‐induced or myogenic renal vasoconstriction by depolarization of VSMC. As inhibition of a single type of K+ channel caused only minor or no renal vasoconstriction in vivo in rats, we hypothesized that several classes of K+ channels must be blocked to achieve sufficient depolarization to elicit renal vasoconstriction. We measured renal blood flow (RBF) in vivo in anesthetized Sprague Dawley rats using an ultrasonic flow probe. Test agents were infused directly into the renal artery to avoid systemic effects. Inhibition of BKCa and Kir channels (with TEA and Ba2+, respectively) caused small and transient reductions of RBF to 93 ± 2 % and 95 ± 1 % of baseline, respectively. KATP, SKCa or Kv channel blockade (with glibenclamide, apamin and 4‐aminopyridine, respectively) was without effect. However, a cocktail of all blockers caused a massive reduction of RBF (down to 15 ± 10 % of baseline after 4 min P < 0.05). Nifedipine abolished this reduction (RBF = 94 ± 3 % of baseline after 4 min; NS vs. baseline). We conclude that inhibition of a single type of K+ channels is not sufficient to elicit renal vasoconstriction. On the other hand it is possible that a diverging mechanism, which affects several K+ channels, plays a role in the regulation of renal hemodynamics. Our results also suggest that the renal vasoconstriction elicited by K+ channel blockade is mediated by nifedipine sensitive Ca2+ channels.