Key result
Pinacidil completely suppressed contractions elicited by isoosmolar K+ Krebs solution, but only weakly inhibited hyperosmolar KCl-induced contractions in guinea-pig smooth muscle preparations.
The relaxant effect of pinacidil on smooth muscle contracted by high potassium depends on the osmolarity of the solution, suggesting mechanisms of action beyond K+ channel opening.
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Osmolarity-dependent pinacidil effects in guinea-pig tissue suggest mechanisms beyond K+ channel opening; leaves open human validation.
Contractions were produced in guinea-pig trachealis, aorta and pulmonary artery by depolarization with 124 mM K+ using two commonly applied techniques. Addition of KCl to the organ bath solution making it hyperosmolar induced slowly developing contractions, which were only weakly inhibited by pinacidil. Hyperosmolar mannitol-induced contractions showed similar characteristics. In contrast, contractions elicited by isoosmolar K+ Krebs solution developed more rapidly and could be completely suppressed by pinacidil (10(-6)-10(-3) M) in a concentration-dependent manner. The findings explain previously published discrepant results on the relaxant response to pinacidil of smooth muscle preparations contracted by high concentrations of K+, and indicate other mechanisms of action for pinacidil in addition to K+ channel opening, in the concentration range 10(-6)-10(-3) M.
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Nielsen‐Kudsk et al. (1990) studied this question. Pinacidil vs. Hyperosmolar vs isoosmolar K+ solutions was evaluated on Relaxant response of smooth muscle preparations. Pinacidil completely suppressed contractions elicited by isoosmolar K+ Krebs solution, but only weakly inhibited hyperosmolar KCl-induced contractions in guinea-pig smooth muscle preparations.
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