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Effect of free running wheel exercise on renal expression of parathyroid hormone receptor type 1 in spontaneously hypertensive rats.

ABSTRACT: An active lifestyle is generally recommended for hypertensive patients to prevent subsequent end-organ damage. However, experimental data on long-term effects of exercise on hypertension are insufficient and underlying mechanisms are not well understood. This study was aimed to investigate the effect of exercise on renal expression of parathyroid hormone-related protein (PTHrP) and parathyroid hormone receptor type 1 (PTHR1) in spontaneously hypertensive rats (SHR). Twenty-four rats started free running wheel exercise at the age of 1.5 months (pre-hypertensive state) and proceeded for 1.5, 3.0, 6.0, and 10.0 months. Thirty rats kept under standard housing conditions were used as sedentary controls. Kidney function was assessed by measuring plasma creatinine levels and urine albumin-to-creatinine ratios. Renal expression of PTHrP and PTHR1 was analyzed by qRT-PCR and western blot. Renal expression of PTHR1 was markedly increased between the 6th and 10th months in sedentary rats and this increase was significantly lower in SHRs with high physical activity on mRNA (-30%) and protein level (-27%). At the same time, urine albumin-to-creatinine ratio increased (from 65 to 231 mg/g) but somehow lower in exercise performing SHRs (48-196 mg/g). Our data suggest that enhanced exercise, stimulated by allocation of a free running wheel, is associated with lower PTHR1 expression in SHRs and this may contribute to preserved kidney function.

SUBMITTER: Braun K

PROVIDER: S-EPMC6129773 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Effect of free running wheel exercise on renal expression of parathyroid hormone receptor type 1 in spontaneously hypertensive rats.

Braun Katja K Atmanspacher Felix F Schreckenberg Rolf R Grgic Ivica I Schlüter Klaus-Dieter KD

Physiological reports 20180901 17

An active lifestyle is generally recommended for hypertensive patients to prevent subsequent end-organ damage. However, experimental data on long-term effects of exercise on hypertension are insufficient and underlying mechanisms are not well understood. This study was aimed to investigate the effect of exercise on renal expression of parathyroid hormone-related protein (PTHrP) and parathyroid hormone receptor type 1 (PTHR1) in spontaneously hypertensive rats (SHR). Twenty-four rats started free ...[more]

PMID: 30198211

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Project description: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.

Project description:Aims:Current antihypertensive therapies cannot cure hypertension and a life-long medication is necessary. Maternal treatment may represent a promising strategy for hypertension treatment. We have previously shown that maternal treatment of spontaneously hypertensive rats (SHR) with pentaerythritol tetranitrate (PETN) leads to a persistent blood pressure reduction in the female offspring. The underlying mechanisms include improved endothelial function resulting from long-lasting epigenetic changes. In the present study, we address the renal effects of maternal PETN treatment. Methods and Results:F0 parental SHR were fed with either normal chow or PETN-containing (1 g/kg) chow ad libitum from the time point of mating to the end of lactation period. The F1 offspring received normal chow without PETN from the time point of weaning (at the age of 3 weeks). At the age of 16 weeks, female PETN offspring showed lower blood pressure than the control. No difference was observed in male offspring. All following experiments were performed with kidneys from 16-week-old female offspring. Maternal PETN treatment reduced the mRNA and protein expression of angiotensin-converting enzyme (ACE) and basic fibroblast growth factor (FGF2), resulting from epigenetic modifications found at the proximal promoter regions. The expression levels of mineralocorticoid receptor (MR) and factors in the MR signalling pathway (Rac1 and Sgk1) were also reduced by PETN. Major profibrotic cytokines, including Wnt4, TNF-alpha, TGF-beta, and MMP9, were downregulated by PETN, which was associated with reduced collagen deposition and glomerulus sclerosis in the kidney of PETN offspring. In addition, PETN treatment also decreased the markers of inflammation and immune cell infiltration in the kidneys. Conclusions:PETN maternal treatment leads to epigenetic changes in the kidney of female SHR offspring. The reduced renal inflammation, alleviated kidney fibrosis, and decreased MR signalling are potential mechanisms contributing to the observed blood pressure-lowering effect.

Project description:BackgroundRadiofrequency ablation of the renal arteries (RF-ABL) has been shown to decrease blood pressure (BP) in drug-resistant hypertensive patients who receive antihypertensive drug therapy. However, there remain questions regarding how RF-ABL influences BP independent of drug therapy and whether complete renal denervation is necessary to maximally lower BP. To study these questions, we examined the cardiovascular, sympathetic, and renal effects produced by RF-ABL of the proximal renal arteries in spontaneously hypertensive rats (SHR) with established hypertension.MethodsSHR were instrumented (telemetry) for measurement of systolic/diastolic BP (SBP/DBP). Rats then underwent Sham-ABL or RF-ABL adjacent to the renal ostium and BP was recorded for 8 weeks. Changes in sympathetic activity, 24-hour water/sodium excretion, and levels of urinary angiotensinogen (AGT), plasma renin activity, and kidney renin content (KRC) were measured in SHR.ResultsCompared with Sham-ABL, RF-ABL produced a sustained decrease in BP. At 8 weeks, SBP/DBP was 171±6/115±3 and 183±4/129±3mm Hg for RF-ABL and Sham-ABL SHR, respectively. Correlating with the reduction in BP, RF-ABL significantly decreased the low frequency/total and low frequency/high frequency of BP variability and attenuated the hypotensive response to chlorisondamine. Kidney norepinephrine levels were markedly decreased at 8 weeks in RF-ABL vs. Sham-ABL SHR. There were no group differences in 24-hour sodium/water excretion or urinary AGT excretion rate (6 weeks) or plasma renin activity or KRC (8 weeks). In other studies, concurrent RF-ABL plus surgical denervation initially decreased BP to a greater level than RF-ABL alone, but thereafter the reduction in BP between groups was not different.ConclusionsIn hypertensive SHR, bilateral RF-ABL of the proximal renal arteries produced a sustained decease in sympathetic activity and BP without changes in sodium/water excretion or activity of the systemic/renal renin-angiotensin system.

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Effect of free running wheel exercise on renal expression of parathyroid hormone receptor type 1 in spontaneously hypertensive rats.

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Effect of free running wheel exercise on renal expression of parathyroid hormone receptor type 1 in spontaneously hypertensive rats.

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