Endogenous dipeptidyl‐peptidase IV modulates skeletal muscle arteriolar diameter in rats

Neuropeptide Y 1‐36 is a potent vasoconstrictor that plays an important role in resistance of smaller arterioles. The enzyme, dipeptidyl‐peptidase IV (DPP‐IV), is present on the smooth muscle cell membrane and converts NPY 1‐36 to its non‐vasoconstricting form, NPY 3‐36 . New research suggests that DPP‐IV is also released from skeletal muscle as a myokine in response to different stimuli including muscle contractions and whey protein supplementation. The role of DPP‐IV as a myokine is unknown. It was hypothesized that whey protein will release DPP‐IV from the muscle and will attenuate neuropeptide Y Y 1 ‐mediated vasoconstriction in skeletal muscle arterioles. The left gluteus maximus (GM) muscle of anesthetized male Sprague‐Dawley rats (n=8) was exposed for intravital video microscopy and superfused with physiological salt solution (5 ml/min; pH 7.4, 35°C). Once a stable baseline was established, the GM arteriolar network was scanned and imaged from 1 st to 6 th order arterioles (1A to 6A). Following baseline imaging, superfusion solution was switched to 100mM whey protein isolate (WPI) dissolved in PSS, to stimulate release of DPP‐IV from the muscle. Imaging of the network was repeated after arteriolar responses stabilized. Next, a DPP‐IV inhibitor (K579; 4μm) was added to the PSS + WPI superfusion and imaging of the GM arteriolar network was repeated. One‐Way ANOVA for each branch of the network was used to determine statistical significance with alpha set at 0.05. When the WPI solution was suffused over the muscle the entire arteriolar network vasodilated. The magnitude of change in arteriolar diameter increased with progressing arteriolar order, where WPI promoted a 14% increase in arteriolar diameter in 1A (p=0.0002), 17% in 3A (p<0.0001), and 23% in 6A (p<0.0001). However, when the DPP‐IV inhibitor was added to the WPI superfusion vasodilation was lost and arteriolar diameters across the network returned to baseline. These findings show that DPP‐IV is released from skeletal muscle in response to topically applied WPI, which has potential to vasodilate skeletal muscle arteriolar networks, likely via conversion of NPY 1‐36 to NPY 3‐36 . Future research should address if muscle contractions increase DPP‐IV secretion from skeletal muscle and affect local blood flow control. Support or Funding Information Funded by NSERC and Western Visiting Scholars Program

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