Adiponectin‐deficient Mice Demonstrate Impaired Coronary Arteriolar Vasodilation and Subsequent Decline in Cardiac Function

Abstract

Circulating adiponectin levels have been shown to correlate with microvascular coronary function, suggesting a cardioprotective effect. Our previous work has shown that adiponectin deficiency decreases coronary smooth muscle contractile function and physiological cardiac hypertrophy that is not reversed with exercise training. However, it is unknown if adiponectin deficiency adversely affects endothelial‐dependent coronary vasodilation, leading to cardiac abnormalities. We tested the hypotheses that adiponectin is necessary for acetylcholine (ACh) and flow‐induced vasodilation in coronary arterioles. It was also hypothesized that exercise training would improve cardiac function in exercise trained wild‐type, but not adiponectin knock‐out (AdipoKO) mice.MethodsC57BL/6 wild‐type (WT) or homozygous AdipoKO mice were obtained at 10 weeks of age and underwent treadmill exercise (12 m/min, 5° incline, 1 hour/day, 5 days/week for 8 weeks) or remained sedentary in cages. At the end of the training/sedentary period, coronary resistance arterioles (intraluminal diameter <150 mm) were isolated, cannulated, and placed under an inverted microscope equipped with a video camera and caliper to record luminal diameter. Vasodilatory responses to ACh (1e‐9 to 1e–4M) and changes in flow (Pressure differences = 2–60 cm H2O) were then assessed. Pre/post cardiac function was measured with a high‐resolution imaging system (Vevo 2100), with M‐mode, and was used to assess ejection fraction, fractional shortening, and left ventricular (LV) mass. Pulsed‐wave Doppler was used to calculate isovolumic relaxation (IVRT)/contraction (IVCT) time.Resultsexercise‐trained WT mice demonstrated physiological cardiac hypertrophy, indicated by a significant increase in LV mass (P<0.05). Exercise‐trained WT mice also had a significantly greater ejection fraction and fractional shortening (both; p<0.05). In contrast, cardiac hypertrophy was absent in exercise‐trained AdipoKO mice and a significant decrease in ejection fraction and fractional shortening was found (both; p>0.05). Further, both sedentary groups were shown to have significant declines in fractional shortening and ejection fraction (p<0.05). Exercise‐training maintained both IVRT/IVCT in the WT mice; however, a significant (p<0.05) lengthening of the IVRT/IVCT was shown in exercise‐trained AdipoKO and WT sedentary mice (p<0.05). The sedentary AdipoKO was shown to have an increase in IVRT only (p<0.05). Sedentary WT mice had significantly greater mean vasodilation to ACh compared to sedentary AdipoKO (p<0.01). Exercise‐training led to increased flow‐induced dilation in the WT (p<0.05), but not the AdipoKO mice (p>0.05).Conclusionthese results indicate that adiponectin is necessary for improvements in cardiac function during exercise training in young adult mice. Additionally, adiponectin may help with preserved cardiac function and that flow‐induced coronary arteriolar vasodilation may have contributed to this response.Support or Funding InformationFSU Research FundsThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.