Obesity does not diminish coronary microvascular function in the Obese Zucker Rat

Obesity is an emerging risk factor for cardiovascular disease documented to impair vascular function in several organ beds. This study hypothesized that obesity decreases vasodilator responses and increases vasoconstrictor responses in the coronary microcirculation. Cardiac function was assessed by in vivo measures of cardiac output. Vascular reactivity of small coronary arteries (~200 μm intraluminal diameter) from lean (LZR) and obese (OZR) Zucker rats was examined in vitro using videomicroscopy. OZR had a larger cardiac mass, stroke volume and cardiac output compared to the LZR. Coronary arteries showed a reduced constrictor response to ET‐1, KCl, with no change in response to serotonin in the OZR (n=10) as compared to the LZR (n=10). Direct activation of PKC with PBDU produced a significantly smaller response at all doses in OZR (n=10). Vasodilation to acetylcholine was completely inhibited by L‐NAME in both LZR and OZR (n=5) and not impaired in the coronary arteries of the OZR. Indeed, maximal responses are potentiated in OZR. Passive mechanics studies showed that the inner diameters of vessels from OZR are larger than the LZR (n=6). The circumferential stress strain relationship was similar in the OZR and the LZR. Thus we conclude that in contrast to our hypothesis and findings in other beds, an increased vasodilator response and a decreased vasoconstrictor response exists in the coronary microvasculature of the OZR. This lack of dysfunction in the presence of obesity and insulin resistance may reflect a reversal/prevention of microvascular dysfunction by the hyperdynamic function of the heart in obese subjects. Supported by NIH R01HL‐76533