Abstract 17167: Uncontrolled Hypertension Increases Endothelin-1-Induced Contractile Response of Coronary Microvasculature Both Before and After Cardioplegia and Cardiopulmonary Bypass

Abstract

Introduction: Hypertensive patients undergoing cardiopulmonary bypass (CPB) have worse clinical outcomes, and coronary microvascular dysfunction may play a role. Endothelin-1 (ET-1), a vasoactive biopeptide, is increased in cardiomyocytes during the hypertrophic response to hypertension and in patients following CPB. Differential effects of hypertension on coronary microvascular reactivity and molecular signaling pathways following CPB have yet to be elucidated. Aims: This study investigated the effects of well-controlled and uncontrolled hypertension on CPB-induced changes in coronary microvascular vasoconstriction to ET-1 and associated signaling using unique in vitro microvascular reactivity studies, RNA deep sequencing, and established molecular methods. Methods: Coronary microvessels (<200um) were harvested from atrial samples from patients with no hypertension (NH), well-controlled hypertension (CH), and uncontrolled hypertension (UH) before and after CPB. In vitro contractile response to ET-1 was assessed using video microscopy. Protein expression and receptor localization were measured using immunoblotting and immunohistochemistry, respectively. Enzyme-linked immunosorbent assay was used to quantify plasma concentration of ET-1. Results: Pre-CPB contractile response of coronary microvessels to ET-1 in UH was increased compared to NH or CH (p <0.05). Post-CPB contractile response was impaired overall (p <0.05). Between groups, contractile response in CH and NH was comparable while response in UH was higher (p <0.05). Plasma ET-1 increased post-CPB (p = 0.18). Total protein levels and localization of ET A R and ET B R were unchanged post-CPB. Conclusions: While CPB overall blunted vasomotor contractile response of coronary microvessels to ET-1, UH was associated with relatively increased vasoconstriction compared to CH and NH. Changes in plasma ET-1, ET A R and ET B R levels or localization did not contribute to these effects.