PS-04-015 Effects of openers of small and intermediate calcium-activated K channels on cardiac rhythm and erectile function in rats

Abstract

Examine the effect of NS309 and NS4591 openers of KCa2.3 (SK) and KCa3.1 (IK) channels, on cardiac rhythm and blood pressure as well as erectile function. Mean arterial pressure (MAP), intracavernosal pressure (ICP) and electrocardiography were measured in anesthetized rats, corpus cavernosum strips were mounted for isometric tension recording and processed for immunoblotting. Erectile function measured as (ICP/MAP) was increased during administration of NS309 and NS4591, while increases in ICP by stimulation of the cavernous nerve were unchanged. Heart sinus node and atrial ventricle conduction changed with an increment in depolarization and conduction, ventricle depolarization increase in association with the heart rate (QTc). Corpus cavernosum relaxation improved upon NS309 and NS4591 administration, and involved activation of SK and large conductance potassium channels (BK). Immunoblotting revealed the presence of SK channels in the corpus cavernosum. Our findings suggest that NS309 and NS4591 improve erectile function during infusion and may restore erectile function in disease. However, the effect on cardiac rhythm needs to be taken into account in the development of drugs of this class with longer duration of action.