Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension

Abstract

Background and purpose: Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (SHR).

Experimental approach: Normotensive Wistar Kyoto (WKY), SHR and SHR trained on a treadmill for 12 weeks were used to evaluate vascular structural, mechanical and functional properties.

Key results: Exercise did not affect lumen diameter, wall thickness and wall/lumen ratio but reduced vascular stiffness of coronary and mesenteric arteries from SHR. Exercise also reduced collagen deposition and normalized altered internal elastic lamina organization and expression of MMP-9 in mesenteric arteries from SHR. Exercise did not affect contractile responses of coronary arteries but improved the endothelium-dependent relaxation in SHR. In mesenteric arteries, training normalized the increased contractile responses induced by U46619 and by high concentrations of acetylcholine. In vessels from SHR, exercise normalized the effects of the NADPH oxidase inhibitor apocynin and the NOS inhibitor l-NAME in vasodilator or vasoconstrictor responses, normalized the increased O(2) (-) production and the reduced Cu/Zn superoxide dismutase expression and increased NO production.

Conclusions and implications: Exercise training of SHR improves endothelial function and vascular stiffness in coronary and small mesenteric arteries. This might be related to the concomitant decrease of oxidative stress and increase of NO bioavailability. Such effects demonstrate the beneficial effects of exercise on the vascular system and could contribute to a reduction in blood pressure.

Figure 1

Exercise training does not affect hypertensive vascular remodelling. Relationships between internal diameter, wall thickness, CSA and wall-to-lumen ratio and intraluminal pressure curves in coronary and small mesenteric arteries from WKY, SHR and SHR trained incubated in 0Ca²⁺-KHS. Coronary arteries, n = 4–7; mesenteric arteries, n = 5–7. Data are means ± SEM. **P < 0.01 versus WKY.

Figure 2

Exercise training does not affect layer thickness and cell number in hypertensive arteries. (A) Adventitia and media thickness and (B) total number of adventitial (AC), smooth muscle (SMC) and endothelial (EC) cells in coronary and small mesenteric arteries from WKY, SHR and SHR trained. Data expressed as mean ± SEM. *P < 0.05, **P < 0.01 versus WKY. n = 3–8.

Figure 3

Exercise training improves vascular mechanical properties in hypertension. Incremental distensibility–intraluminal pressure and stress–strain relationships in coronary and small mesenteric resistance arteries from WKY, SHR and SHR trained incubated in 0Ca²⁺-KHS. Coronary arteries, n = 4–7; mesenteric arteries, n = 5–8. Data are means ± SEM. *P < 0.05, **P < 0.01 versus WKY; †P < 0.05 versus SHR.

Figure 4

Exercise training normalizes ECM proteins in mesenteric arteries from hypertensive rats. (A) Representative images and respective quantification of collagen staining (Picrosirius Red) of transverse sections obtained from small mesenteric arteries from WKY, SHR and SHR Trained (n = 4–6). Bars indicates 50 μm. (B) Representative confocal projections of the internal elastic lamina and quantitative analysis of the area of fenestrae and total number of fenestrae in the internal elastic lamina from small mesenteric arteries of WKY, SHR and SHR Trained (n = 5–7). Projections were obtained from serial optical sections captured with a fluorescence confocal microscope (×63, oil immersion objective; zoom, ×2). Image size 119 × 119 μm. (C) Densitometric analysis and representative Western blots of MMP-2, MMP-9 and GAPDH protein expression in homogenates of small mesenteric arteries from WKY, SHR and SHR Trained (n = 5–6). Data are means ± SEM. *P < 0.05, **P < 0.01 versus WKY; †P < 0.05 versus SHR.

Figure 5

Exercise training normalizes vascular contraction by increasing NO production and/or bioavailability. (A) Concentration–response curve to U46619 and (B) effect of l-NAME (100 μM) on the concentration–response curve to U46619 in small mesenteric arteries from WKY, SHR and SHR Trained (n = 4–15). (C) Representative fluorescent microphotographs of confocal microscopy images of NO production in the absence or in the presence of l-NAME of small mesenteric arteries from SHR and SHR Trained. Projections were obtained from serial optical sections captured with a fluorescence confocal microscope (×40, oil immersion objective; zoom, ×1). Image size 375 × 375 μm. Quantitative analysis of NO production is also shown (n = 8). (D) Plasma nitrite levels from WKY, SHR and SHR Trained (n = 5–9). (E) Densitometric analysis and representative blots of eNOS protein expression in mesenteric arteries from WKY, SHR and SHR Trained. GAPDH is also shown (n = 7–9). Data are means ± SEM. **P < 0.01 versus WKY. †P < 0.05, ††P < 0.01 versus SHR. #P < 0.05, ##P < 0.01 versus Control.

Figure 6

Exercise training normalizes vascular contraction by decreasing production of O₂⁻ and/or bioavailability. (A) Effect of apocynin (300 μM) on the concentration–response curve to U46619 in small mesenteric arteries from WKY, SHR and SHR Trained (n = 6–15). (B) Representative fluorescent microphotographs of confocal microscopy images and quantitative analysis of O₂⁻ production from small mesenteric arteries from WKY, SHR and SHR Trained. Image size 238 × 238 μm (n = 5–8). (C) Effect of apocynin on O₂⁻ production in small mesenteric arteries from SHR. Image size 375 × 375 μm (n = 5). (D) Densitometric analysis and representative Western blot of Cu/Zn-SOD, Mn-SOD and EC-SOD protein expression in homogenates of small mesenteric arteries from WKY, SHR and SHR Trained. The expression of GAPDH is shown as the loading control (n = 5–7). Data are means ± SEM. *P < 0.05, **P < 0.01 versus WKY. †P < 0.05, ††P < 0.01 versus SHR. #P < 0.05, ##P < 0.01 versus Control.

Figure 7

Exercise training reduces endothelial dysfunction by increasing NO bioavailability. (A) Concentration–response curves to ACh and diethylamine NONOate (DEA-NO) in coronary arteries from WKY, SHR and SHR Trained. Effect of l-NAME (100 μM) and apocynin (300 μM) on the concentration–response curve of ACh in coronary arteries from WKY (B), SHR (C) and SHR Trained (D) (n = 4–14). Representative fluorescent microphotographs of confocal microscopy images and quantitative analysis of O₂⁻ production in coronary arteries from SHR in the absence (Control) and in the presence of apocynin in also shown in panel B. Image size 375 × 375 μm (n = 4). **P < 0.01 versus WKY. ††P < 0.01 versus SHR. # P < 0.05, ##P < 0.01 versus control.

Figure 8

Exercise training decreases the participation of endothelium-dependent vasoconstrictor factors on ACh responses. Concentration–response curves to ACh in small mesenteric arteries pre-contracted with phenylephrine (A) or U46619 (B) from WKY, SHR and SHR Trained. (C) Concentration–response curve to diethylamine NONOate (DEA-NO) in small mesenteric arteries pre-contracted with U46619 from WKY, SHR and SHR Trained. *P < 0.05 versus WKY. †P < 0.05 versus SHR. n = 4–8.