The effects of acute and chronic exercise on the vasculature

Abstract

Regular physical activity (endurance training, ET) has a strong positive link with cardiovascular health. The aim of this review is to draw together the current knowledge on gene expression in different cell types comprising the vessels of the circulatory system, with special emphasis on the endothelium, and how these gene products interact to influence vascular health. The effect beneficial effects of ET on the endothelium are believed to result from increased vascular shear stress during ET bouts. A number of mechanosensory mechanisms have been elucidated that may contribute to the effects of ET on vascular function, but there are questions regarding interactions among molecular pathways. For instance, increases in flow brought on by ET can reduce circulating levels of viscosity and haemostatic and inflammatory variables that may interact with increased shear stress, releasing vasoactive substances such as nitric oxide and prostacyclin, decreasing permeability to plasma lipoproteins as well as the adhesion of leucocytes. At this time the optimal rate-of-flow and rate-of-change in flow for determining whether anti-atherogenic or pro-atherogenic processes proceed remain unknown. In addition, the impact of haemodynamic variables differs with vessel size and tissue type in which arteries are located. While the hurdles to understanding the mechanism responsible for ET-induced alterations in vascular cell gene expression are significant, they in no way undermine the established benefits of regular physical activity to the cardiovascular system and to general overall health. This review summarizes current understanding of control of vascular cell gene expression by exercise and how these processes lead to improved cardiovascular health.

Figure 1

Local control of arterial blood flow in skeletal muscle during exercise (see text for details). (A) Myogenic response: blood pressure results in stretching of the vessel wall circumference. (B) Conducted response: vascular signalling by release of acetylcholine, for example. Other putative signalling involves K_ATP channels, although their location (on endothelial, vascular smooth muscle or skeletal muscle cells) is not yet defined (Murrant & Sarelius 2000). (C) Flow-mediated response: fluid shear stress due to longitudinal blood flow. (D) Metabolic response: chemical release by red blood cells and skeletal muscle, generating an upstream vasomotor signal. (E) Endothelial-mediated responses at the cellular level (image not to scale). NO, nitric oxide; eNOS, endothelial nitric oxide synthase; PGI₂, prostacyclin; ACh, acetylcholine; sGC, soluble guanylate cyclase; EDHF, endothelium-derived hyperpolarizing factor; COX, cyclooxygenase; AC, adenylate cyclase.

Figure 2

Cellular and molecular effects of exercise-induced shear stress. Under conditions of prolonged laminar flow ① increase in Na-K-Cl co-transporter expression leads to ② EDHF-type-mediated vasodilation. ③ Membrane lipids as mechanotransducers. ④ Glycocalyx-mediated stimulation of caveolae-bound eNOS, producing NO. ⑤ Integrin phosphorylation and activation of non-receptor tyrosine kinase cascade. ⑥ Phosphoinositide-3-kinase (PI3K)-dependent pathways for phosphorylation of eNOS. ⑦ Flow-mediated activation of heterotrimeric G proteins. ⑧ Release of NO and PGI₂ as vasodilators and anti-platelet mediators. ⑨ Leucocyte recruitment and binding to the endothelium in areas of low or turbulent shear stress. ⑨ Expression of vasoconstrictor endothelin-1 (ET-1) under conditions of reduced or turbulent flow. AA, arachidonic acid; Cox, cyclooxygenase; eNOS, endothelial nitric oxide synthase; ECE, endothelin-converting enzyme; EDHF, endothelial-derived hyperpolarizing factor; , gene transcription; ICAM1, intercellular adhesion molecule 1; KLF2, Krüppel-like factor 2; MAPK, mitogen-activated protein kinase; Nrf2, nuclear factor erythroid 2-like 2; PGI₂, prostacyclin; sGC, soluble guanylate cyclase; TFs, transcription factors.