Evaluation of Hindlimb Arteriolar Vasodilation Evoked by Dynamic Muscle Contraction in Goto‐Kakizaki Rats Using in vivo X‐ray Microangiography

Abstract

Vascular endothelial dysfunction is a well established comorbidity in diabetes mellitus. In peripheral resistance arteries, it has been reported that endothelium‐dependent hyperpolarization (EDH), which is an important factor to induce vasodilation in small arteries, is downregulated in diabetic animals. We hypothesized that downregulation of EDH inhibits exercise‐induced vasodilation in diabetic patients and causes exercise intolerance. To test this hypothesis, the objective of this study was to evaluate peripheral vascular function in response to muscle contraction and the contribution of EDH to vasodilation in anesthetized diabetic rats. Type 2 diabetic Goto‐Kakizaki (GK) rat and healthy Wistar rat were anesthetized by urethane + α‐chloralose, and then mechanically ventilated. Carotid artery and jugular vein were cannulated for monitoring blood pressure and administering pharmaceutical agents. By means of X‐ray angiography, the hindlimb vasculature was visualized by infusing iodine contrast agent via the catheter inserted into the femoral artery. Angiography was performed before and after rhythmic muscle contraction (0.5 s tetanic contraction + 0.5 s relaxation, repeated 30 times) evoked by sciatic nerve stimulation (40 Hz, 0.1 ms duration). Femoral blood flow was simultaneously monitored by a transit‐time ultrasonic flowmeter. To investigate the contribution of EDH to the changes in arterial diameter and vessel recruitment, angiography was repeated after an intravenous administration of small conductance and big conductance potassium channel inhibitors (50 μg/kg apamin+charybdotoxin), which are known to suppress the EDH‐dependent vasodilation.We observed increases in arterial diameter (~100% increase) in most of hindlimb arteries after the muscle contraction except for the superficial artery and the saphenous artery. We also observed recruitment of small arteries (diameter less than 100 μm), which were not visualized at baseline condition. These vasodilative effects on the hindlimb arteries were similar in GK rat compared to Wistar rat. Increase in femoral blood flow at peak and decrease in vascular resistance at the nadir were also similar between the groups. Inhibition of potassium channels did not affect baseline diameter in arteries and the changes in vasodilation after muscle contraction in either Wistar or GK rats. In conclusion, effects of acute muscle contraction on the changes in arterial diameter and recruitment were preserved in the GK rat. EDH may not contribute to induce the peak response in arterial diameter after muscle contraction.Support or Funding InformationThis work was supported by Grants‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [18K10882].