Exercise, but not perivascular fat, effects coronary artery vasomotor function in a familial hypercholesterolemic (FH) porcine atherosclerosis model

Abstract

Our lab has shown that left circumflex coronary artery (LCX) PAT blunts endothelin‐1 (ET‐1) induced maximal (max) contractions in normal pigs on low and high fat diets. Other studies report that PAT exerts anti‐contractile effects on agonist‐induced arterial contraction via release of a relaxing factor that acts on the underlying vasculature. The purpose of this study was to test the hypotheses that: PAT blunts LCX contraction in FH pigs and that EX augments this anti‐contractile effect. Male FH pigs were divided into EX (n=13) and sedentary (SED) (n=15) groups. LCX reactivity to angiotensin II (AngII), bradykinin (BK), ET‐1, and sodium nitroprusside (SNP) was evaluated in vitro, with intact or removed PAT (+/‐PAT). LCX relaxation induced by BK and SNP was not altered by EX or ‐PAT. AngII‐induced max LCX contraction was nearly 2‐fold higher in EX than SED +PAT (p=0.1275). There was no difference between SED and EX responses to AngII ‐PAT rings. ET‐1 induced max contraction of LCX was not different between SED ‐PAT and SED +PAT, or between EX ‐PAT and EX +PAT. LCX from SED pigs exhibited a greater ET‐1 induced max contraction than LCX from EX pigs (p<0.05). We conclude that while PAT had no effect on LCX agonist‐induced contractions, EX did act to blunt ET‐1 induced max contractions in LCX +PAT and ‐PAT. (NIH HL‐52490)