Abstract
Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.
Highlights
An active lifestyle is recommended to reduce the risk of new onset of hypertension and disease progression in hypertensives
We first compared the levels of mRNA expression of uncoupling proteins (UCPs), glucose transporters, and proprotein convertase subtilisin/kexin 9 (PCSK9) between the M. gastrocnemius, M. soleus, liver, visceral, and subcutaneous fat tissue (Figure 1)
Fat tissue are the most important regulators of metabolism, we studied the expression of UCP-2 and UCP-3, GLUT-1, GLUT-4, and PCSK9 in these tissues under basal conditions and under constitutively high physical activity performed by free running wheel exercise for 10 months
Summary
An active lifestyle is recommended to reduce the risk of new onset of hypertension and disease progression in hypertensives. Beneficial side effects of exercise are improvements of lipid and glucose metabolism. Skeletal muscle, and fat tissue are important organs regarding metabolism, effects of exercise on metabolism should result in molecular adaptations of these organs. A gene variant in the UCP-3 promoter region that is linked to the regulation of UCP2 is associated with improved energy efficiency during exercise. This indicates the relationship between UCPs and exercisedependent adaptation of metabolism (Buemann et al, 2001). A better understanding of these processes in the presence of co-morbidities such as hypertension or obesity is required to optimize non-pharmacological interventions
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