Voluntary physical exercise and coronary flow velocity reserve: a transthoracic colour Doppler echocardiography study in spontaneously hypertensive rats

Abstract

In the present study, we have developed and demonstrated a coronary artery imaging protocol in rats using transthoracic high-frequency CDE (colour Doppler echocardiography) to investigate the potential direct effects of exercise on CFVR (coronary flow velocity reserve). SHR (spontaneously hypertensive rats) performed voluntary exercise for 6 weeks. Rats were then submitted to ultrasonographic examination and CFVR measurements. The LAD (left anterior descending coronary artery) was visualized using transthoracic CDE in a modified parasternal long-axis view. Doppler measurement was made in mid-LAD during baseline and adenosine-induced hyperaemic condition. Gene and protein expression in cardiac tissue were studied using real-time PCR and immunohistochemistry. Adenosine infusion significantly (P<0.001, as determined by ANOVA) decreased HR, without affecting blood pressure in anaesthetized SHR. A significantly greater adenosine dose-dependent response was seen in exercised rats compared with controls (P=0.02, as determined by ANOVA). The baseline flow velocity in mid-LAD was 0.33+/-0.06 and 0.41+/-0.14 m/s in the exercised and control animals respectively (P value was not significant). The maximum adenosine-induced response was reached at a dose of 140 microg.kg-1 of body weight.min-1, and CFVR averaged at 2.6+/-0.53 and 1.5+/-0.24 in exercised and control animals respectively (P<0.01). Gene expression of CuZnSOD was up-regulated by 21% in exercised animals compared with controls (1.1+/-0.16 compared with 0.89+/-0.09; P<0.01), whereas eNOS expression was unchanged. In conclusion, CFVR in rats can be non-invasively assessed using CDE with high feasibility. Physical exercise is associated with improved CFVR and antioxidative capacity in SHR.

Interaction between exercise and hypertension in spontaneously hypertensive rats: a meta-analysis of experimental studies

“…Beneficial effects that have been described are a decrease in oxidative stress, 5,6 an increase of cytochrome oxidase activity in cardiac mitochondria, 7 a fall in blood pressure, 8,9 normalization of calcium-handling proteins, 10,11 delayed hypertrophyassociated fetal gene shifts, 12 improvement of endothelium-dependent vasorelaxation, 13,14 induction of antiapoptotic genes 15,16 and improved b-adrenoceptor coupling. 17 In contrast, a normalization of calcium-handling proteins was not observed by others, 7 nor was a fall in blood pressure, 18 a change in the function of cardiomyocytes, 19 or a change in heart function.…”

Coronary flow responses to exercise training: further evidence of the benefit of an underutilized therapeutic modality

“…Gene and protein expression in cardiac tissue were assessed using immunohistochemistry and realtime PCR. The authors [7] found significantly greater adenosine-induced hyperaemia in exercising rats compared with controls, with a 2.6-fold increase in velocity in exercised animals compared with a 1.5 times increase in the controls. These changes were matched by increased gene expression of superoxide dismutase, without a change of endogenous nitric oxide synthase.…”

“…The weight of evidence suggests that these beneficial effects are probably mediated through improvements in vascular function, perhaps through replenishment of the endothelium by circulating endothelial progenitor cells released during exercise [5]. Although much interest has focused on peripheral vascular function, Hambrecht et al [6] have proposed effects on coronary vascular function in patients with coronary artery disease and, in this issue of Clinical Science, Hägg and co-workers [7] propose a coronary artery effect in an animal model without coronary disease.…”

“…The concerns that clinicians often express about animal models are applicable to the study by Hägg et al [7]: the effect could relate to the animal selected (whose vasculature may not parallel that of humans), the different physiological responses of a relatively acute model compared with chronically abnormal coronary arteries, and the difficulty in delivering an equivalent intensity of exercise to patients with cardiovascular disease in 'real life'. Nonetheless, the consistency of the findings Comment with existing clinical studies [6], and the associated gene and protein studies suggest this is a plausible phenomenon.…”

“…In the study by Hägg et al [7], spontaneously hypertensive rats were exercised for 6 weeks, and the effects of exercise training were studied using transthoracic Doppler evaluation of left anterior descending artery flow at rest and in response to adenosine-induced hyperaemia. Gene and protein expression in cardiac tissue were assessed using immunohistochemistry and realtime PCR.…”