Vasoplegia and endothelial dysfunction are well-known complications of cardioplegia and cardiopulmonary bypass (CP/CPB). Our lab has previously shown that endothelial adherens junction impairment is driven by vascular endothelial (VE)-cadherin phosphorylation. In this study we investigate the interplay of hypertension and CP/CPB.

Right atrial tissue was harvested pre- and post-CP/CPB from patients undergoing surgery. Patients were stratified into nonhypertensive, controlled hypertension, and uncontrolled hypertension groups based on history and in-office blood pressure measurements. Atrial tissue was sent for transcriptomics. Expression, phosphorylation, and localization of VE-cadherin was assessed by immunoblotting and immunohistochemistry. Atrial microvascular reactivity to adenosine diphosphate was assessed by videomicroscopy.

Several genes related to reactive oxygen species handling, nitric oxide signaling, and adherens junctions were suppressed in patients with uncontrolled hypertension versus nonhypertensive patients pre-CP/CPB. By immunoblotting, patients with uncontrolled hypertension had significantly higher levels of phosphorylated VE-cadherin (p-VE cadherin) and higher ratios of p-VE cadherin/VE-cadherin compared with nonhypertensive (P < .05). Perivascular p-VE cadherin density by immunofluorescence was higher in patients with uncontrolled hypertension compared with nonhypertensive patients and patients with controlled hypertension (P < .05). There were significant decreases in vasodilatory response to adenosine diphosphate after CP/CPB (P < .05) in patients with uncontrolled hypertension compared with nonhypertensive patients. Patients with uncontrolled hypertension had significantly higher increases in weight on postoperative day 1 compared with nonhypertensive patients (P < .05).

Our study supports a 2-hit model in which hypertension primes the endothelium for dysfunction, and CP/CPB amplifies this injury through impaired reactive oxygen species handling, nitric oxide dysregulation, and adherens junction destabilization. These findings highlight the importance of preoperative hypertension management to improve postoperative outcomes.