Aerobic exercise-induced inhibition of PKCα/CaV1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension

Yu Chen; Yanyan Zhang; Meiling Shan; Yang Zhou; Yanjun Huang; Lijun Shi

doi:10.1016/j.abb.2019.108191

Aerobic exercise-induced inhibition of PKCα/Ca_V1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension

Arch Biochem Biophys. 2019 Dec 15:678:108191. doi: 10.1016/j.abb.2019.108191. Epub 2019 Nov 13.

Authors

Yu Chen¹, Yanyan Zhang², Meiling Shan², Yang Zhou², Yanjun Huang², Lijun Shi³

Affiliations

¹ Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China; China Institute of Sport and Health Science, Beijing Sport University, Beijing, 100084, China.
² Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China.
³ Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China; Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, 100084, China. Electronic address: l_j_shi72@163.com.

PMID: 31733216
DOI: 10.1016/j.abb.2019.108191

Abstract

Regular exercise is regarded as a nonpharmacological therapy for controlling hypertension by improving the function of vascular smooth muscle cells (VSMCs). The underlying mechanism is unclear. L-type-voltage-dependent Ca²⁺ channel (Ca_V1.2) on the plasma membrane and PKCα of VSMCs are pivotal modulators of vascular tone. PKCα is hyperactivated and concentrated at the surface membrane during hypertension. This study investigated the effects of aerobic exercise on the PKCα and Ca_V1.2 in mesenteric arterial smooth muscle cells from spontaneously hypertensive rats (SHRs). SHRs and Wistar-Kyoto (WKY) rats were randomly assigned into sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Exercise groups were performed a 12-week moderate-intensity (18-20 m/min) treadmill training. Mesenteric arterial mechanical and functional properties were evaluated. Exercise reduced body weight and systolic blood pressure in both SHR-EX and WKY-EX. PDBu (PKC activator) and BayK 8644 (Ca_V1.2 agonist) elicited vasoconstriction, while Gö6976 (PKCα inhibitor) and nifedipine (Ca_V1.2 blocker) induced vasodilation of the vessel rings. In SHRs, exercise normalized the increased vascular sensitivity to these activators and inhibitors. Nifedipine greatly suppressed PDBu-induced vasoconstriction. Upon incubation with Gö6976, the effects of both PDBu and nifedipine were markedly suppressed. In patch-clamp studies, PDBu increased and Gö6976 decreased the Ca_V1.2 current density. Exercise ameliorated the responses of both PDBu and Gö6976 in SHRs. Immunofluorescence staining suggested that exercise training alleviated the hypertension-induced increase of colocalization rate of PKCα and Ca_V1.2 α_1C subunit in VSMCs. These data indicate that hypertension enhanced PKCα/Ca_V1.2 pathway-induced constriction of mesenteric arteries, and this pathological enhancement is inhibited by aerobic exercise training.

Keywords: Aerobic exercise; Hypertension; Mesenteric artery; PKCα/ Ca(V)1.2 pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aerobiosis
Animals
Blood Pressure
Body Weight
Calcium Channels, L-Type / metabolism*
Hypertension / metabolism
Hypertension / pathology
Hypertension / physiopathology*
Male
Mesenteric Arteries / physiopathology*
Physical Conditioning, Animal*
Protein Kinase C-alpha / metabolism*
Rats
Vasodilation*

Substances

Calcium Channels, L-Type
Protein Kinase C-alpha