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

Michelini, Lisete Compagno

doi:10.1007/s11906-007-0039-x

Cited by 42 publications

(51 citation statements)

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“…These changes significantly correlated with training-induced reductions in resting HR. A long cascade of events elicits these effects, triggered by an increase in pressure during repetitive exercise: 1) increased afferent signaling to the NTS (7), 2) increased noradrenergic drive from NTS to PVN preautonomic neurons (18), 3) structural remodeling of trained PVN preautonomic neurons that exhibit stronger dendritic branching and a larger surface area compared with sedentary controls (29), 4) increased OT mRNA expression in the PVN and substantial augmentation of peptide density within parvocellular PVN OTergic neurons (present data in trained intact controls), 5) increased intrinsic excitability, specifically in PVN-NTS-projecting neurons, with diminished input-output function in PVN magnocellular neurons that project to the neurohypophysis (20), 6) augmented OTergic projections from the PVN to the NTS/DMV complex in trained individuals (23,26), 7) facilitated vagal outflow to the heart during OTergic stimulation (16,27), and 8) resting bradycardia in both trained WKY and SHR rats, which correlated with peptide content within OTergic preautonomic neurons (present study).…”

Section: Discussionmentioning

confidence: 83%

“…A series of studies indicated that low-intensity aerobic training in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats improved afferent signaling by aortic baroreceptors (7) and increased noradrenergic drive from the brain stem to hypothalamic preautonomic neurons (18). Training also caused structural remodeling and increased the intrinsic excitability of oxytocinergic (OTergic) and vasopressinergic (VPergic) neurons within the paraventricular nucleus (PVN) of the hypothalamus that project to the brain stem (20,29), thus activating OTergic and VPergic drive to dorsal brain stem areas (23,26,29). Oxytocinergic input is involved in the modulation of vagal outflow to the heart, causing resting bradycardia and smaller exercise tachycardia in trained WKY and SHR rats (6,16,17,25).…”

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confidence: 99%

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Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Cavalleri

Burgi

Cruz

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Michelini LC. Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity. Am J Physiol Regul Integr Comp Physiol 301: R958 -R966, 2011. First published July 27, 2011 doi:10.1152/ajpregu.00104.2011.-We showed previously that oxytocinergic (OTergic) projections from the hypothalamic paraventricular nucleus (PVN) to the dorsal brain stem mediate traininginduced heart rate (HR) adjustments and that beneficial effects of training are blocked by sinoaortic denervation (SAD; Exp Physiol 94: 630 -640; 1103-1113). We sought now to determine the combined effect of training and SAD on PVN OTergic neurons in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Rats underwent SAD or sham surgery and were trained (55% of maximal capacity) or kept sedentary for 3 mo. After hemodynamic measurements were taken at rest, rats were deeply anesthetized. Fresh brains were frozen and sliced to isolate the PVN; samples were processed for OT expression (real-time PCR) and fixed brains were processed for OT immunofluorescence. In sham rats, training improved treadmill performance and increased the gain of baroreflex control of HR. Training reduced resting HR (Ϫ8%) in both groups, with a fall in blood pressure (Ϫ10%) only in SHR rats. These changes were accompanied by marked increases in PVN OT mRNA expression (3.9-and 2.2-fold in WKY and SHR rats, respectively) and peptide density in PVN OTergic neurons (2.6-fold in both groups), with significant correlations between OT content and training-induced resting bradycardia. SAD abolished PVN OT mRNA expression and markedly reduced PVN OT density in WKY and SHR. Training had no effect on HR, PVN OT mRNA, or OT content following SAD. The chronic absence of inputs from baroreceptors and chemoreceptors uncovers the pivotal role of afferent signaling in driving both the plasticity and activity of PVN OTergic neurons, as well as the beneficial effects of training on cardiovascular control. sinoaortic denervation; exercise training; hypothalamus; paraventricular nucleus; supraoptic nucleus; oxytocin; spontaneous hypertension ACCUMULATING EXPERIMENTAL evidence from our and other laboratories has shown that aerobic training promotes several beneficial cardiovascular effects in normotensive and hypertensive individuals. Training causes remodeling of the heart with a simultaneous stroke volume increase and heart rate (HR) decrease (5, 34, 40), outward eutrophic remodeling of arterioles, capillary angiogenesis, and venule neoformation in the exercised muscles (1-3, 10, 24). Exercise training is also accompanied by a predominance of relaxation over contractile endothelium-derived factors (15, 44). These adaptive mechanisms by improving blood flow and tissue conductance, by reducing vascular resistance, and restoring normal endothelial function favor the amelioration of impaired functions in cardiovascular disease.Training reduces both the activity of the renin-angiotensin system and oxidative stress (13,22,38) and effectively induces neuronal pla...

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Section: Discussionmentioning

confidence: 83%

mentioning

confidence: 99%

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Cavalleri

Burgi

Cruz

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…of ascending/descending pathways that integrate bulbar and hypothalamic areas involved in cardiovascular control. For a comprehensive understanding of the central effects on autonomic pathways in both normotensive and hypertensive individuals the reader is referred to other excellent papers and reviews (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Effect of gender on training-induced vascular remodeling in SHR

Amaral

Michelini

2011

Braz J Med Biol Res

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There is accumulating evidence that physical inactivity, associated with the modern sedentary lifestyle, is a major determinant of hypertension. It represents the most important modifiable risk factor for cardiovascular diseases, which are the leading cause of morbidity and mortality for both men and women. In addition to involving sympathetic overactivity that alters hemodynamic parameters, hypertension is accompanied by several abnormalities in the skeletal muscle circulation including vessel rarefaction and increased arteriole wall-to-lumen ratio, which contribute to increased total peripheral resistance. Low-intensity aerobic training is a promising tool for the prevention, treatment and control of high blood pressure, but its efficacy may differ between men and women and between male and female animals. This review focuses on peripheral training-induced adaptations that contribute to a blood pressure-lowering effect, with special attention to differential responses in male and female spontaneously hypertensive rats (SHR). Heart, diaphragm and skeletal muscle arterioles (but not kidney arterioles) undergo eutrophic outward remodeling in trained male SHR, which contributed to a reduction of peripheral resistance and to a pressure fall. In contrast, trained female SHR showed no change in arteriole wall-to-lumen ratio and no pressure fall. On the other hand, training-induced adaptive changes in capillaries and venules (increased density) were similar in male and female SHR, supporting a similar hyperemic response to exercise.

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“…The functional consequences of these distinct stage-dependent responses need to be interpreted through the location and role of these brain-stem nuclei in the blood pressure control circuit. The NTS is known to be the primary site of cardiorespiratory regulatory integration (1,8,9,13,33,46,47). The RVLM receives inhibitory projections from the caudal ventrolateral medulla.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA network changes in the brain stem underlie the development of hypertension

DeCicco

Zhu

Brureau

et al. 2015

Physiological Genomics

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sion is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 wellannotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage-and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.hypertension; microRNA; neuroinflammation; angiotensin II; brain stem HYPERTENSION IS A MAJOR CHRONIC disease worldwide, affecting about 50 million adults in the United States alone. It is a multiorgan disease and a major cause of heart failure, coronary heart disease, atrial fibrillation, stroke, and end-stage renal disease, and it has an enormous economic impact. About 90 -95% of cases are "essential" with no known medical cause (11). Moreover, only about a third of hypertensive patients have their blood pressure fully controlled (11). A significant and increasing population (ϳ25%) of hypertensive patients is drug resistant. There remains an unmet need for antihypertensive therapy.In the context of the recent discovery of novel lines of therapeutic interventions involving approaches to modulate microRNA we decided to elucidate changes in microRNA levels during the development of spontaneous hypertensive rat (SHR) hypertension. The recent explosion in microRNA research has produced new computational and experimental approaches for studying microRNA functions in cell culture and in vivo, which we take advantage of here. MicroRNAs are an abundant class of small (ϳ22 nt) endogenous noncoding RNAs that direct posttranscriptional regulation of gene expression. There is ample evidence that dysregulation of microRNAs is associated with the pathogenesis of human diseases, in...

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

Cited by 42 publications

References 52 publications

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Afferent signaling drives oxytocinergic preautonomic neurons and mediates training-induced plasticity

Effect of gender on training-induced vascular remodeling in SHR

MicroRNA network changes in the brain stem underlie the development of hypertension

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