swimming-exercise-protocol-and-care-methods-for-pregnant-rats

Swimming Exercise Protocol and Care Methods for Pregnant Rats

The developmental origins of health and disease concept highlights the impact of early environments on chronic non-communicable diseases like diabetes, ...

effect-maternal-aerobic-exercise-on-myocardial-cerebral

Effect of Maternal Aerobic Exercise on Myocardial and Cerebral Ischemia/Reperfusion Injury in Offspring of Hypertensive Rats

Hypertension-mediated organ damage (HMOD) affects vital organs such as the heart and brain, leading to adverse outcomes and posing a serious threat to ...

Beijing Sport University

Regular exercise is regarded as a nonpharmacological therapy for controlling hypertension by improving the function of vascular smooth muscle cells (VSMCs). The underlying mechanism is unclear. L-type-voltage-dependent Ca channel (Ca1.2) on the plasma membrane and PKCα of VSMCs are pivotal modulators of vascular tone. PKCα is hyperactivated and concentrated at the surface membrane during hypertension. This study investigated the effects of aerobic exercise on the PKCα and Ca1.2 in mesenteric arterial smooth muscle cells from spontaneously hypertensive rats (SHRs). SHRs and Wistar-Kyoto (WKY) rats were randomly assigned into sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Exercise groups were performed a 12-week moderate-intensity (18-20 m/min) treadmill training. Mesenteric arterial mechanical and functional properties were evaluated. Exercise reduced body weight and systolic blood pressure in both SHR-EX and WKY-EX. PDBu (PKC activator) and BayK 8644 (Ca1.2 agonist) elicited vasoconstriction, while Gö6976 (PKCα inhibitor) and nifedipine (Ca1.2 blocker) induced vasodilation of the vessel rings. In SHRs, exercise normalized the increased vascular sensitivity to these activators and inhibitors. Nifedipine greatly suppressed PDBu-induced vasoconstriction. Upon incubation with Gö6976, the effects of both PDBu and nifedipine were markedly suppressed. In patch-clamp studies, PDBu increased and Gö6976 decreased the Ca1.2 current density. Exercise ameliorated the responses of both PDBu and Gö6976 in SHRs. Immunofluorescence staining suggested that exercise training alleviated the hypertension-induced increase of colocalization rate of PKCα and Ca1.2 α subunit in VSMCs. These data indicate that hypertension enhanced PKCα/Ca1.2 pathway-induced constriction of mesenteric arteries, and this pathological enhancement is inhibited by aerobic exercise training.

Aerobic exercise-induced inhibition of PKCα/Ca1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension.

The angiotensin II signaling system regulates vascular dysfunction and is involved in the programming of hypertension. Maternal exercise has been linked to both short-term and long-term benefits for the mother and fetus. However, the impacts of maternal exercise on the intravascular renin-angiotensin system (RAS) in hypertensive offspring remain unexamined. This study examined whether maternal exercise has an epigenetic effect in repressing angiotensin II type 1 receptor (ATR) expression, which leads to favorable alterations in the mesenteric artery (MA) function of spontaneously hypertensive offspring. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) pregnant rats were randomly divided into an exercise group and a control group. Blood pressure, vascular tone, ATR protein and mRNA expression, and ATR gene (Agtr1a) promoter methylation status were examined in the MAs of 3-month-old male offspring. Maternal exercise significantly reduced the resting blood pressure and cardiovascular reactivity of offspring from SHRs. Furthermore, Ang II-ATR activity in regulating vascular tone and ATR expression was decreased in the MAs of the SHR offspring from the exercise groups. Importantly, exercise during gestation suppressed ATR expression via hypermethylation of the Agtr1a promoter region and upregulated DNA methyltransferase (DNMT) expression in MAs of SHR offspring. These results suggest that maternal exercise upregulates DNMT expression, resulting in hypermethylation and repression of the Agtr1a gene, which may prevent MA dysfunction in the offspring of SHRs. A mechanistic model on the epigenetics of exercise during pregnancy. Maternal exercise during pregnancy triggers hypermethylation and transcriptional suppression of the Agtr1a gene via increased DNMT1 and DNMT3B expression in MAs of SHR offspring. Downregulation of AT1R expression reduces the contribution of Ang II to vascular tone, ultimately improving vascular structure and function. VSMC vascular smooth muscle cell; Ang II angiotensin II; AT1aR angiotensin type 1 receptor (AT1R) alpha subtypes; Agtr1a AT1R alpha isoform gene; MAs mesenteric arteries; BP blood pressure.

Maternal exercise upregulates the DNA methylation of Agtr1a to enhance vascular function in offspring of hypertensive rats.

Maternal exercise during pregnancy has emerged as a potentially promising approach to protect offspring from cardiovascular disease, including hypertension. Although endothelial dysfunction is involved in the pathophysiology of hypertension, limited studies have characterized how maternal exercise influences endothelial function of hypertensive offspring. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were assigned either to a sedentary lifestyle or to swimming training daily, and fetal histone deacetylase-mediated epigenetic modification and offspring vascular function of mesenteric arteries were analyzed. Maternal exercise ameliorated the impairment of acetylcholine-induced vasodilation without affecting sodium nitroprusside-induced vasodilation in mesenteric arteries from the hypertensive offspring. In accordance, maternal exercise reduced NADPH oxidase-4 (Nox4) protein to prevent the loss of nitric oxide generation and increased reactive oxygen species production in mesenteric arteries of hypertensive offspring. We further found that maternal exercise during pregnancy upregulated vascular SIRT1 (sirtuin 1) expression, leading to a low level of H3K9ac (histone H3 lysine 9 acetylation), resulting in the transcriptional downregulation of Nox4 in mesenteric arteries of hypertensive fetuses. These findings show that maternal exercise alleviates oxidative stress and the impairment of endothelium-dependent vasodilatation via SIRT1-regulated deacetylation of Nox4, which might contribute to improved vascular function in hypertensive offspring.

Maternal exercise represses Nox4 via SIRT1 to prevent vascular oxidative stress and endothelial dysfunction in SHR offspring.

Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism by which myocyte AKAP150 (A-kinase anchoring protein 150) inhibition induced by exercise training alleviates voltage-dependent L-type Ca channel (Ca1.2) activity and restores cerebral arterial function in hypertension.

Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of Ca1.2 Channel Function in Cerebral Arteries of Hypertensive Rats.

Maternal exercise during pregnancy is widely recognized as an effective means of promoting cardiovascular health in offspring. Few studies have explored how maternal exercise impacts vascular function and phenotypic switching in hypertensive offspring, despite the known involvement of vascular structural and functional remodeling in hypertension pathogenesis. Research indicates a significant relationship between elevated blood pressure and fibroblast growth factor 21 (FGF21) levels. It remains unclear whether maternal exercise during pregnancy can improve vascular function in hypertensive offspring by regulating FGF21 and its underlying mechanisms. In this study, pregnant spontaneously hypertensive rats and Wistar-Kyoto rats were randomly assigned to either a sedentary or exercise group. The exercise group underwent weightless swimming exercise from gestation day 1 (GD1) to GD20. The aim was to investigate the epigenetic modifications mediated by histone deacetylase sirtuin 1 (SIRT1) during the fetal period and the phenotypic changes in the mesenteric arteries (MAs) of hypertensive offspring. We found that maternal exercise significantly improved vascular remodeling in hypertensive offspring. Specifically, maternal exercise upregulated SIRT1 expression, which led to decreased H3K9ac (histone H3 lysine 9 acetylation) in the promoter region of the FGF21 gene. This epigenetic modification resulted in the transcriptional downregulation of FGF21 in the MAs of hypertensive fetuses. These results suggest that maternal exercise may lower blood pressure in hypertensive offspring by regulating deacetylation of the FGF21 gene promoter region through SIRT1, thereby reversing phenotypic switching and vascular structural remodeling.

ArticleTotal : 2	Year
Publication title Cited by 2	2024
Publication title	2025

Article	Year
Aerobic exercise-induced inhibition of PKCα/Ca1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension. Archives of biochemistry and biophysics\| PubMed ID: 31733216	2019
Maternal exercise upregulates the DNA methylation of Agtr1a to enhance vascular function in offspring of hypertensive rats. Hypertension research : official journal of the Japanese Society of Hypertension\| PubMed ID: 36539461	2023
Maternal exercise represses Nox4 via SIRT1 to prevent vascular oxidative stress and endothelial dysfunction in SHR offspring. Frontiers in endocrinology\| PubMed ID: 37501791	2023
Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of Ca1.2 Channel Function in Cerebral Arteries of Hypertensive Rats. Arteriosclerosis, thrombosis, and vascular biology\| PubMed ID: 38602101	2024
Maternal exercise represses FGF21 via SIRT1 to improve the phenotypic transformation of vascular smooth muscle in hypertensive offspring. Hypertension research : official journal of the Japanese Society of Hypertension\| PubMed ID: 39543417	2025

Meiling Shan

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