SKA‐31, a positive modulator of SKCa and IKCa channels, increases systemic conductance and lowers arrterial pressure in an anesthetized pig model

Abstract

SKA‐31 regulates microvascular tone, tissue perfusion and blood pressure by acting on endothelial SKCa and IKCa channels. In this study, we have examined the hemodynamic effects of SKA‐31 in comparison to the established vasodilator sodium nitroprusside (SNP) in anesthetized domestic pigs. We measured left ventricular (LV), aortic and inferior vena cava (IVC) pressures and monitored levels of blood flow in the ascending aorta, right carotid, left anterior descending coronary and left renal arteries during acute intravenous infusions of SKA‐31 (0.1 to 5 mg/kg), followed by a single dose of SNP (5 μg/kg). SKA‐31 dose‐dependently and reversibly decreased mean aortic pressure (mPAO) to a level comparable to that produced by SNP (−23±3 vs. −28±4 mmHg). Mean IVC pressure did not change. Both SKA‐31 (1 to 5 mg/kg doses) and SNP increased systemic conductance, along with coronary and carotid artery conductances; renal conductance did not change. There was no change in LV stroke volume (SV) for any infusion, and heart rate was not altered following SKA‐31 administration (132±14 vs. 128±13 bpm). With no change in SV, the significant decrease in LV stroke work (SW) observed with either SKA‐31 or SNP was largely attributed to decreased mPAO. In summary, SKA‐31 significantly decreased mPAO by increasing systemic conductance, and did not appear to reduce cardiac contractility. Supported by the CIHR (JVT and APB) and the NIH (HW).