Enalapril induces muscle epigenetic changes and contributes to prevent a decline in running capacity in spontaneously hypertensive rats.

Drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can improve muscle function and exercise capacity, as well as preventing, attenuating or reversing age-related losses in muscle mass, however, the exact mechanisms by which these drugs affect muscle cells, are not yet fully elucidated. Moreover, the potential epigenetic alterations induced in skeletal muscle tissue are also largely unexplored. The aim of this study was to evaluate if enalapril or losartan can change the physical performance and epigenetic profile of skeletal muscle in spontaneously hypertensive rats (SHRs).

Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats.

Aging is accompanied by considerable deterioration of homeostatic systems, such as autonomic imbalance characterized by heightened sympathetic activity, lower parasympathetic tone, and depressed heart rate (HR) variability, which are aggravated by hypertension. Here, we hypothesized that these age-related deficits in aged hypertensive rats can be ameliorated by exercise training, with benefits to the cardiovascular system. Therefore, male 22-mo-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) submitted to moderate-intensity exercise training (T) or kept sedentary (S) for 8 wk were evaluated for hemodynamic/autonomic parameters, baroreflex sensitivity, cardiac sympathetic/parasympathetic tone and analysis of dopamine β-hydroxylase (DBH+) and oxytocin (OT+) pathways of autonomic brain nuclei.

Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model.

Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H buffering, regulation of Ca transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function.

The Cholinergic Drug Galantamine Alleviates Oxidative Stress Alongside Anti-inflammatory and Cardio-Metabolic Effects in Subjects With the Metabolic Syndrome in a Randomized Trial.

The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements.

Training-Induced Deactivation of the AT Receptor Pathway Drives Autonomic Control and Heart Remodeling During the Transition From the Pre- to Hypertensive Phase in Spontaneously Hypertensive Rats.

Background: The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated.

Methods and results: Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls.

The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats.

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats.

Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas-The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats.

Background: Exercise training (T) blunts functional deficits and renin-angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular-controlling areas.

Aerobic training normalizes autonomic dysfunction, HMGB1 content, microglia activation and inflammation in hypothalamic paraventricular nucleus of SHR.

Exercise training (ExT) is recommended to treat hypertension along with pharmaceutical antihypertensive therapies. Effects of ExT in hypothalamic content of high mobility box 1 (HMGB1) and microglial activation remain unknown. We examined whether ExT would decrease autonomic and cardiovascular abnormalities in spontaneously hypertensive rats (SHR), and whether these effects were associated with decreased HMGB1 content, microglial activation, and inflammation in the hypothalamic paraventricular nucleus (PVN).

Influence of aerobic training on the reduced vasoconstriction to angiotensin II in rats exposed to intrauterine growth restriction: possible role of oxidative stress and AT2 receptor of angiotensin II.

Intrauterine growth restriction (IUGR) is associated with impaired vascular function, which contributes to the increased incidence of chronic disease. The aim of this study was to investigate whether aerobic training improves AngII-induced vasoconstriction in IUGR rats. Moreover, we assess the role of superoxide dismutase (SOD) isoforms and NADPH oxidase-derived superoxide anions in this improvement.

Training-induced pressure fall in spontaneously hypertensive rats is associated with reduced angiotensinogen mRNA expression within the nucleus tractus solitarii.

Knowing that exercise training reduces arterial pressure in hypertensive individuals and that pressure fall is accompanied by blockade of brain renin-angiotensin system, we sought to investigate whether training (T) affects central renin-angiotensin system. Spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto controls (WKY) were submitted to training or kept sedentary (S) for 3 months. After functional recordings, brain was removed and processed for autoradiography (brain stem sequential slices hybridized with (35)S-oligodeoxynucleotide probes for angiotensinogen [Aogen] and angiotensin II type 1 [AT(1A)] receptors).

The NTS and integration of cardiovascular control during exercise in normotensive and hypertensive individuals.

Due to upward resetting of baroreceptors, tachycardia coexists with increased pressure during dynamic exercise. This review critically evaluates current knowledge of proposed mechanisms to explain the continuous resetting of baroreflex control of heart rate and sympathetic nerve activity during and after exercise and exercise training. Of interest is the exercise-induced upward resetting that occurs in hypertensive and normotensive individuals.

Differential effects of vasopressinergic and oxytocinergic pre-autonomic neurons on circulatory control: reflex mechanisms and changes during exercise.

1. The role of vasopressinergic and oxytocinergic (VPergic and OTergic, respectively) projections to the brain stem in the modulation of heart rate control is discussed on the basis of both changes in the peptide content of the dorsal brain stem (DBS) and functional effects following reflex- and exercise-induced activation in the presence and/or absence of receptor blockade within the nucleus tractus solitarius (NTS) and/or peripheral autonomic block. 2.

Training-induced, pressure-lowering effect in SHR: wide effects on circulatory profile of exercised and nonexercised muscles.

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.