Neuropeptide Y1 and alpha-1 adrenergic receptor-mediated decreases in functional vasodilation in gluteus maximus microvascular networks of prediabetic mice.

Nicole M Novielli-Kuntz,Dwayne N Jackson,Kent A Lemaster,Jefferson C Frisbee

doi:10.14814/phy2.13755

Nicole M Novielli-Kuntz, Dwayne N Jackson + Show 2 more

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https://doi.org/10.14814/phy2.13755

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Journal: Physiological Reports	Publication Date: Jul 1, 2018
Citations: 1	License type: cc-by

Affiliation: Western University

Abstract

Prediabetes is associated with impaired contraction‐evoked dilation of skeletal muscle arterioles, which may be due to increased sympathetic activity accompanying this early stage of diabetes disease. Herein, we sought to determine whether blunted contraction‐evoked vasodilation resulted from enhanced sympathetic neuropeptide Y1 receptor (Y1R) and alpha‐1 adrenergic receptor (α1R) activation. Using intravital video microscopy, second‐, third‐, and fourth‐order (2A, 3A, and 4A) arteriolar diameters were measured before and following electrical field stimulation of the gluteus maximus muscle (GM) in prediabetic (PD, Pound Mouse) and control (CTRL, c57bl6, CTRL) mice. Baseline diameter was similar between groups; however, single tetanic contraction (100 Hz; 400 and 800 msec) and sustained rhythmic contraction (2 and 8 Hz, 30 sec) evoked rapid onset vasodilation and steady‐state vasodilatory responses that were blunted by 50% or greater in PD versus CTRL. Following Y1R and α1R blockade with sympathetic antagonists BIBP3226 and prazosin, contraction‐evoked arteriolar dilation in PD was restored to levels observed in CTRL. Furthermore, arteriolar vasoconstrictor responses to NPY (10−13–10−8 mol/L) and PE (10−9–10−5 mol/L) were greater in PD versus CTRL at higher concentrations, especially at 3A and 4A. These findings suggest that contraction‐evoked vasodilation in PD is blunted by Y1R and α1R receptor activation throughout skeletal muscle arteriolar networks.

Highlights

IntroductionPeripheral vascular complications associated with type 2 diabetes (Creager et al 2003) are initiated in the prediabetic state, before manifestation of chronic diabetes disease, where the initiation of vascular dysfunction occurs in the distal microvasculature
Upon blocking sympathetic receptors with BIBP3226 (Y1R antagonist; 100 nmol/L) and prazosin (a1R antagonist; 100 nmol/L) during simultaneous SNP (10 lmol/L) superfusion, maximal vasodilatory responses in PD 2A and 3A recovered to CTRL levels (Table 2)
We demonstrated that heightened constitutive activation of Y1 receptor (Y1R) and a1R contributes to compromised rapid onset vasodilation (ROV) and steady-state vasodilation in response to tetanic and rhythmic muscle contractions throughout skeletal muscle arteriolar networks in prediabetic mice

Summary

Introduction

Peripheral vascular complications associated with type 2 diabetes (Creager et al 2003) are initiated in the prediabetic state, before manifestation of chronic diabetes disease, where the initiation of vascular dysfunction occurs in the distal microvasculature. Prediabetes is a condition of elevated blood glucose, insulin resistance, and hyperinsulinemia that occurs prior to pancreatic b-cell failure and overt type 2 diabetes. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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