Training-Induced, Pressure-Lowering Effect in SHR

Abstract

Abstract-We showed that the training-induced, pressure-lowering effect correlates with decreased arteriole wall/lumen ratio and venule growth in the gracilis muscle. To investigate whether these beneficial changes are tissue-specific or occur in other muscles and tissues, we analyzed the effects of hypertension and training on microcirculatory profile of locomotor/nonlocomotor muscles and another nonmuscular tissue. Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were submitted to low-intensity training (50% to 60% maximal exercise capacity, 13 weeks); age-matched control rats were kept sedentary. Trained and sedentary rats were instrumented for pressure and heart rate measurements at rest. Morphometric analyses (arterioles, capillaries, venules) were performed in all tissues. Training attenuated pressure and heart rate only in SHR. Arterioles (inner diameter Ͻ30 m) were markedly hypertrophied in sedentary SHR, but wall/lumen ratio was equally reduced (Ϸ30%) and normalized by training in locomotor (soleus, gastrocnemius, gracilis) and nonlocomotor skeletal muscles (temporalis) in the myocardium and diaphragm, without changes in the renal cortex. Training also increased venule density (Ϸ2-fold) only in locomotor and nonlocomotor muscles of SHR. Capillary density was similarly increased in all exercised muscles of both groups, with no change in temporalis and kidneys. Data suggest that growth/proliferation of small venules and regression of hypertrophied arteriole wall/lumen ratio are generalized tissue-specific (skeletal muscle) and group-specific (SHR) adjustments to training to reduce local resistance and augment physical capacity of circulation, thus contributing to training-induced pressurelowering effect. They are accompanied by remodeling of myocardium (cardiac output) and diaphragm arterioles (ventilatory adjustments), stressing the importance of training as a nonpharmacological therapy to control pressure levels in hypertension. Key Words: life style Ⅲ hypertension, chronic Ⅲ arterioles Ⅲ capillaries Ⅲ myocardium Ⅲ kidney C hronic hypertension is a highly prevalent disease (affecting 20% of adults and Ϸ50% of elderly) and a common risk factor for different cardiovascular diseases. The search for efficient pharmacological and nonpharmacological antihypertensive therapies is a goal pursued by many researchers and clinicians. 1-3 Experimental evidence has shown that regular physical activity reduces pressure in hypertensive patients, contributing to the decrease cardiovascular morbidity and mortality rates. 3,4 However, very little information on the mechanisms underlying the beneficial effects of repetitive exercise is available.In two recent well-controlled studies on male spontaneously hypertensive rats (SHR), 5,6 we confirmed the efficacy of low-intensity aerobic training to reduce pressure levels, showing in addition that pressure reduction was significantly correlated with both hind limb resistance decrease and normalization of the enlarged arteriole wall-to-lumen ratio, presented by the gr...

Effect of gender on training-induced vascular remodeling in SHR

“…Indeed, Moreno et al (27) reported a high kidney weight in female hypertensive rats (vs normotensive controls), which could be a useful "intermediate phenotype" of hypertension. These observations agree with pressure measurements obtained by us and by others: male SHR had higher pressure levels than female SHR (range of 170-185 vs 150-160 mmHg for males and females, respectively) (22,25,26). In general, sex differences have not been extensively explored, since most of the studies were done with male animals.…”

“…In spontaneously hypertensive rats (SHR), the best known experimental model for essential or primary hypertension in humans, we confirmed that high blood pressure levels are accompanied by remodeling of arterioles (increased wall-to-lumen ratio) and capillary rarefaction in many tissues including the skeletal muscles, in which we demonstrated a normal resting blood flow, besides the altered vascular structure (22)(23)(24)(25)(26). According to Mulvany (16), vascular remodeling in hypertension is characterized by increased wall-to-lumen ratio of arteries and arterioles, being classified as eutrophic (decrease in both lumen and outer diameter, with unaltered wall thickness or cross-sectional area) or hypertrophic (increase in media thickening, that encroaches on the lumen).…”

“…Mulvany (16) also postulated that remodeling of small arterioles in SHR is mainly associated with a eutrophic rather than hypertrophic mechanism. Accordingly, we have previously shown that high blood pressure in male SHR is maintained by eutrophic remodeling of arterioles since we observed an increased wall-to-lumen ratio without changes in wall thickness in the kidney, heart, diaphragm, and in locomotor and non-locomotor muscles (22,25). Eutrophic remodeling in the resistance arteries is the most prevalent vascular adjustment to hypertension (20) and could be explained by a combination of growth and apoptotic processes to maintain the media volume (15).…”

“…While male rats exhibited an increased wall-to-lumen ratio of small arterioles in all territories such as skeletal muscles, diaphragm, myocardium, and kidney (22,25), female SHR showed no change in wall-tolumen ratio in many tissues, with a marked increase in the renal arterioles (26). Indeed, Moreno et al (27) reported a high kidney weight in female hypertensive rats (vs normotensive controls), which could be a useful "intermediate phenotype" of hypertension.…”

Effect of long-term physical exercise on blood pressure in African Americans

“…People who can maintain a regular regimen of activity that is of longer duration or of more vigorous intensity are likely to derive greater health benefits than individuals who lead sedentary lives of physical inactivity which is considered to be the strongest individual risk factor for poor health (63). Exercise and lifestyle changes as therapeutic interventions for successfully managing symptoms of hypertension have been found to be efficacious in previous controlled studies (32, 41,44,69,70,71). For instance, aerobic exercise can be valuable in the treatment of mild to moderate essential hypertension because it may cause a decrease in both SBP and DBP.…”