305 - Differences in potassium channel-independent effects of pinacidil on the isolated human saphenous veins obtained from diabetic and non-diabetic patients (ID 419)
Abstract
Background and Aims
Pinacidil is well known potassium (K+) channel opener which relaxes blood vessels trough opening ATP-dependent K+ (KATP) channels located in the plasma membrane of smooth muscle cells. However, numerous in vitro studies were reported K+ channels-independent effects of pinacidil. Therefore, objective of this study was to investigate K+ channels-independent component of pinacidil-induced vasorelaxation on isolated human saphenous vein (HSV) obtained from patients with and without type-2 diabetes mellitus.
Methods
Rings of HSV, without endothelium, obtained from patients undergoing coronary bypass surgery, were mounted in organ bath system and isometric tension was being recorded. The experiments followed multiple curve design. Pinacidil (0.01 – 100 μM) was used for vasorelaxation of HSV precontracted with phenylephrine (100 μM in the presence of normal Krebs-Ringer solution) or solution with 80 mM K+.
Results
In the presence of normal Krebs-Ringer solution, pretreatment with nickel (300 μM), Na+-Ca2+ exchanger inhibitor, or with nifedipine (1 μM), inhibitor of voltage-gated Ca2+ channels, did not inhibited pinacidil effect on HSV obtained from diabetic patients. The same treatment on HSV from non-diabetic patients indicated that nifedipin caused inhibition of pinacidil effects (P < 0.05). However, in the presence of 80 mM K+, pretreatment with nickel or nifedipine antagonized significantly the effect of pinacidil (P < 0.01, both).
Conclusions
Pinacidil endothelium-independent vasorelaxation of HSV from diabetic and non-diabetic patients includes KATP channels-independent effects. In K+ channel-independent component of the pinacidil-induced vasorelaxation, Na+-Ca2+ exchanger and voltage-gated Ca2+ channels are partly involved. However, we have to investigate further additional K+ channel-independent mechanism(s) of pinacidil.
