Predator Scent-Induced Sensitization of Hypertension and Anxiety-like Behaviors

Xue, Baojian; Xue, Jiarui; Yu, Yang; Wei, Shun-Guang; Beltz, Terry G.; Felder, Robert B.; Johnson, Alan Kim

doi:10.1007/s10571-020-01005-y

Cited by 15 publications

(5 citation statements)

References 60 publications

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“…In addition, voluntary exercise has been demonstrated to induce less stress when compared with those forced exercise such as forced treadmill running or swimming ( Billman et al, 2015 ). Forced exercise was not chosen as the method for this study because the psychological stress has been demonstrated to induce the HTRS in our previous studies ( Xue et al, 2019 ; Xue et al, 2020a ).…”

Section: Discussionmentioning

confidence: 99%

Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II

et al. 2022

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Exercise training has profound effects on the renin-angiotensin system, inflammatory cytokines and oxidative stress, all of which affect autonomic nervous system activity and regulate blood pressure (BP) in both physiological and pathophysiological states. Using the Induction-Delay-Expression paradigm, our previous studies demonstrated that various challenges (stressors) during Induction resulted in hypertensive response sensitization (HTRS) during Expression. The present study tested whether voluntary exercise would protect against subpressor angiotensin (ANG) II-induced HTRS in rats. Adult male rats were given access to either “blocked” (sedentary rats) or functional running (exercise rats) wheels for 12 weeks, and the Induction-Delay-Expression paradigm was applied for the rats during the last 4 weeks. A subpressor dose of ANG II given during Induction produced an enhanced hypertensive response to a pressor dose of ANG II given during Expression in sedentary rats in comparison to sedentary animals that received saline (vehicle control) during Induction. Voluntary exercise did not attenuate the pressor dose of ANG II-induced hypertension but prevented the expression of HTRS seen in sedentary animals. Moreover, voluntary exercise reduced body weight gain and feed efficiency, abolished the augmented BP reduction after ganglionic blockade, reversed the increased mRNA expression of pro-hypertensive components, and upregulated mRNA expression of antihypertensive components in the lamina terminalis and hypothalamic paraventricular nucleus, two key brain nuclei involved in the control of sympathetic activity and BP regulation. These results indicate that exercise training plays a beneficial role in preventing HTRS and that this is associated with shifting the balance of the brain prohypertensive and antihypertensive pathways in favor of attenuated central activity driving sympathetic outflow and reduced BP.

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Section: Discussionmentioning

confidence: 99%

Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II

et al. 2022

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“…Voluntary wheel-running exercise was selected to minimize any stressful effects of forced exercise since exogenous or psychological stressors can induce HTRS. 29,30 This yielded 8 control/experimental groups: (1) sedentary normotensive-dam+LFD-offspring, (2) running normotensive-dam+LFD-offspring, (3) sedentary normotensive-dam+HFD-offspring, (4) running normotensive-dam+HFD-offspring, (5) sedentary hypertensive-dam+LFD-offspring, (6) running hypertensive-dam+LFD-offspring, (7) sedentary hypertensive-dam+HFD-offspring, (8) running hypertensive-dam+HFD-offspring. Each experimental group was composed of individual subjects that were randomly selected from different litters.…”

Section: Methodsmentioning

confidence: 99%

Voluntary Exercise Eliminates Maternal Gestational Hypertension–Induced Hypertensive Response Sensitization to Postweaning High-Fat Diet in Male Adult Offspring

Xue

Beltz

et al. 2022

Hypertension

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Background: Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. The present study tested whether voluntary exercise would protect male offspring against maternal gestational hypertension-induced hypertensive response sensitization elicited by post-weaning high-fat diet (HFD). Methods And Results: On low-lard-fat diet, offspring of both normotensive and hypertensive dams had comparable resting blood pressure, but HFD feeding elicited an enhanced increase in blood pressure (ie, hypertensive response sensitization) in sedentary offspring of hypertensive dams when compared with sedentary offspring of normotensive dams. The HFD fed sedentary offspring of hypertensive dams displayed greater sympathetic activity, enhanced pressor responses to centrally administered ANG II (angiotensin II) or leptin, and greater mRNA expression of proinflammatory cytokines, leptin, and a marker of blood-brain barrier leakage in the hypothalamic paraventricular nucleus. The enhanced blood pressure and central sympathetic activity in HFD-fed sedentary offspring of hypertensive dams were significantly reduced by exercise but fell only to levels comparable to HFD-fed exercising offspring of normotensive dams. HFD-induced increases in plasma IL-6 (interleukin-6) and sympathetic activity and greater pressor responses to central TNF (tumor necrosis factor)-α in offspring from both normotensive and hypertensive dams were also maintained after exercise. Nevertheless, exercise had remarkably beneficial effects on metabolic and autonomic function, brain reactivity to ANG II and leptin and gene expression of brain prohypertensive factors in all offspring. Conclusions: Voluntary exercise plays a beneficial role in preventing maternal hypertension-induced hypertensive response sensitization, and that this is associated with attenuation of enhanced brain reactivity and centrally driven sympathetic activity.

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“…and we have not yet found stimuli that can be characterized as stressors (ie, challenges that are considered aversive) that do not result in HTRS in male animals. As noted in this table, classes of stressors identified as physiological (also known as systemic, homeostatic, interoceptive) stressors 18,[38][39][40] and as psychosocial (also known as psychological, processive, neurogenic, mental, exteroceptive) stressors [41][42][43] can induce a state that will manifest as HTRS when presented with a subsequent challenge. The difference between the two classes of stress-associated stimuli is that physiological stressors involve challenges that signal attendant dyshomeostasis (trauma, pain, inflammation, elevated stress hormones) and those that are psychosocial stressors do not immediately disrupt homeostasis but rather pose the possibility of eventual threat to physiological or psychological integrity.…”

Section: Cross-sensitization Of the Hypertensive Responsementioning

confidence: 99%

Sensitization of Hypertension: The Impact of Earlier Life Challenges: Excellence Award for Hypertension Research 2021

Xue

Johnson

2023

Hypertension

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Hypertension affects over 1 billion individuals worldwide. Because the cause of hypertension is known only in a small fraction of patients, most individuals with high blood pressure are diagnosed as having essential hypertension. Elevated sympathetic nervous system activity has been identified in a large portion of hypertensive patients. However, the root cause for this sympathetic overdrive is unknown. A more complete understanding of the breadth of the functional capabilities of the sympathetic nervous system may lead to new insights into the cause of essential hypertension. By employing a unique experimental paradigm, we have recently discovered that the neural network controlling sympathetic drive is more reactive after rats are exposed to mild challenges (stressors) and that the hypertensive response can be sensitized (ie, hypertensive response sensitization [HTRS]). We have also found that the induction of HTRS involves plasticity in the neural network controlling sympathetic drive. The induction and maintenance of the latent HTRS state also require the functional integrity of the brain renin-angiotensin-aldosterone system and the presence of several central inflammatory factors. In this review, we will discuss the induction and expression of HTRS in adult animals and in the progeny of mothers with prenatal obesity/overnutrition or with maternal gestational hypertension. Also, interventions that reverse the effects of stressor-induced HTRS will be reviewed. Understanding the mechanisms underlying HTRS and identifying the beneficial effects of maternal or offspring early-life interventions that prevent or reverse the sensitized state can provide insights into therapeutic strategies for interrupting the vicious cycle of transgenerational hypertension.

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Predator Scent-Induced Sensitization of Hypertension and Anxiety-like Behaviors

Cited by 15 publications

References 60 publications

Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II

Voluntary Exercise Prevents Hypertensive Response Sensitization Induced by Angiotensin II

Voluntary Exercise Eliminates Maternal Gestational Hypertension–Induced Hypertensive Response Sensitization to Postweaning High-Fat Diet in Male Adult Offspring

Sensitization of Hypertension: The Impact of Earlier Life Challenges: Excellence Award for Hypertension Research 2021

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