Impaired contractile response of human peripheral arterioles to angiotensin II after cardiopulmonary bypass

Abstract

Introduction: Vasoplegia is a well-established risk after cardiopulmonary bypass. Angiotensin II is a polypeptide integral to blood pressure and intravascular volume regulation, yet limited evidence explores angiotensin II in post-cardiopulmonary bypass vasoplegia. This study aims to investigate microvascular functional and mechanistic changes to angiotensin II response after cardiopulmonary bypass.

Methods: Skeletal muscle samples were collected from the left internal mammary bed before and after cardiopulmonary bypass in patients undergoing cardiac surgery. Skeletal muscle arterioles were dissected and mounted on microvessel arrays, and internal diameter changes in response to angiotensin II were noted by videomicroscopy. Paired skeletal muscle tissue was sent for deep RNA sequencing per third-party company protocol, and angiotensin II type 1 and type2 receptor expression was quantified by immunoblotting.

Results: Microvascular constriction to angiotensin II in microvessels isolated from skeletal muscle (n = 7) was significantly attenuated in post-cardiopulmonary bypass vessels (P < .05 at 10^-8 [M], 5 × 10^-8 [M], 5 × 10^-7 [M], and 10^-6 [M], P < .01 at 10^-7 [M]). Twelve paired pre-cardiopulmonary bypass and post-cardiopulmonary bypass samples used for deep transcriptomics demonstrated decreased RNA transcripts of G_q/11, a G-protein involved in angiotensin II type 1 receptor-mediated vasoconstriction, in post-cardiopulmonary bypass tissue. There were no significant differences in angiotensin II receptor expression by immunoblotting.

Discussion: These novel findings demonstrate a significant decrease in functional microvascular response to angiotensin II after cardiopulmonary bypass, which may explain postoperative vasoplegia and blood pressure dysregulation. Although there were no changes in angiotensin II receptor expression, changes in G-protein-related signaling may explain this diminished response.