Obesity leads to altered vasomotor function in juvenile Ossabaw pigs

Abstract

Obesity is known to impair endothelial cell‐dependent (ECD) vasodilation, but the effects on vasoconstriction have not been fully elucidated. Currently, there are conflicting reports as to whether agonist‐induced contractile force and kinetics are specifically altered in obesity. We hypothesized that juvenile obesity in Ossabaw pigs alters vasomotor function. Female Ossabaw pigs (5–6 wks of age, N=4–6 rings from 2–3 pigs) were fed with either a low fat diet (3.03 kcal/g, lean control) or a high‐fat/ high‐fructose/high cholesterol diet (4.14kcal/g, obese) for 16 wks and vasomotor function assessed by myography. In distal sections of left anterior descending (LAD) artery, contractile force in response to U‐46619 was impaired (20.0±6.4 vs. 56.9±2.4mN) in obese, despite ECD vasodilation to bradykinin, and EC‐independent vasodilation to sodium nitroprusside being unaffected. In regard to kinetics, time to reach max contraction following addition of U‐46616 was longer in LAD from obese pigs (2232.5±56.1 vs. 804±118.7sec). Furthermore, max contraction by 80mM KCl was reduced in obese pigs compared to lean controls (48.5±1.6 vs. 57.9±1.1mN). Collectively, diet‐induced obesity may lead to an early defect in contractile function as opposed to vasodilation in coronary circulation of juvenile Ossabaw pigs. (Supp: NIH HL085119, VHA‐CDA2IK2BX001299–01, Mizzou Advantage, and the Allen Foundation)