Baroreflex Modulation During Acute High-Altitude Exposure in Rats

Abstract

Baroreflex (BR) control is critically dependent of sympathetic and parasympathetic modulation. It has been documented that during acute hypobaric hypoxia there is a BR control impairment, however, the effect of a natural hypoxic environment on BR function is limited and controversial. Therefore, the aim of this study was to determine the effect of acute High-Altitude exposure on sympathetic/parasympathetic modulation of BR control in normal rats. Male Sprague Dawley rats were randomly allocated into Sea-Level ( n = 7) and High-Altitude ( n = 5) (3,270 m above sea level) groups. The BR control was studied using phenylephrine (Phe) and sodium nitroprusside (SNP) through sigmoidal analysis. The autonomic control of the heart was estimated using heart rate variability (HRV) analysis in frequency domain. Additionally, to determine the maximum sympathetic and parasympathetic activation of BR, spectral non-stationary method analysis, during Phe (0.05 μg/mL) and SNP administration (0.10 μg/mL) were used. Compared to Sea-Level condition, the High-Altitude group displayed parasympathetic withdrawal (high frequency, 0.6–2.4 Hz) and sympathoexcitation (low frequency, 0.04–0.6 Hz). Regarding to BR modulation, rats showed a significant decrease ( p < 0.05) of curvature and parasympathetic bradycardic responses to Phe, without significant differences in sympathetic tachycardic responses to SNP after High-Altitude exposure. In addition, the non-stationary analysis of HRV showed a reduction of parasympathetic activation (Phe) in the High-Altitude group. Our results suggest that acute exposure to High-Altitude produces an autonomic and BR control impairment, characterized by parasympathetic withdrawal after 24 h of high-altitude exposure.

Editorial: Adaptive response of living beings to extreme environments: Integrative approaches from cellular and molecular biology, biotechnology, microbiology to physiology

“…In our Research Topic, Lang et al showed that in hypertensive miners ( n = 10) high altitude was the main factor affecting cardiac autonomic modulation, independently of hypertension. Of note, apparently, the parasympathetic arm of the autonomic nervous system was more affected by high altitude, similar to previous observations ( Beltran et al, 2020 ). Importantly, Lang et al also showed that hypertension was associated with reduced physical performance independently from altitude reached with a higher respiratory frequency.…”

“…Natural conditions, such as high altitude, high gravity, extreme pressures, radiation, cold, heat, salinity, oligotrophic, and others, are examples of stressful factors that challenge the physical and chemical limits at which life can persevere. Among higher organisms, physiological manifestations such as cardiorespiratory adjustments for oxygen homeostasis are adaptive strategies allowing humans to work and live at high altitudes ( Beltran et al, 2020 ; Mallet et al, 2021 ; Lang et al ). Along with this, some human activities are performed in severe environmental conditions, such as diving, and races during extreme heat and cold, among others, which demonstrate the human capacity to push their limits to be able to respond and adapt to conditions where human life would be a great challenge ( Arce-Alvarez, et al, 2021 ; Arce-Alvarez, et al, 2022 ).…”

Ethnic Differences on Cardiac Rhythms and Autonomic Nervous System Responses During a High-Altitude Trek: A Pilot Study Comparing Italian Trekkers to Nepalese Porters

“…However, combining pharmacological inhibition of sympathetic and/or parasympathetic control of the heart, Siebenmann et al demonstrated reduced cardiac parasympathetic activity as the main mechanisms underlying the increase of resting heart rate in response to middle-term exposure to altitude hypoxia (Siebenmann et al, 2017 ). The same evidence was reported in rats, with a parasympathetic withdrawal after 24 h of exposure to 3,270 m above sea level (Beltrán et al, 2020 ). A few evidence exists about ethnic differences in the autonomic control of the cardiovascular response to altitude hypoxia; e.g., altered muscle sympathetic nerve activity and beneficial lower sympathetic vasoconstrictor activity have been suggested as beneficial hypoxic adaptations in Sherpas (Simpson et al, 2019 ).…”

“…Indeed, it can be supposed that, before the trek started, participants had greater arousal and stress with respect to bBC. After the base camp circuit, albeit participants were tested at the same altitude as bBC, the hypobaric hypoxia exposure, along with the physical conditioning, posed a high stressor on participants, determining a chronic sympathetic activation and parasympathetic deactivation, as previously reported (Siebenmann et al, 2017;Beltrán et al, 2020). Considering reduced cardiac parasympathetic activity as the main mechanisms underlying the increase of resting heart rate in response to middle-term exposure to altitude hypoxia (Siebenmann et al, 2017), and that HRV metrics could be considered more adequate in estimate parasympathetic, rather than sympathetic, dynamics (Fontolliet et al, 2018;Thomas et al, 2019), all in all, HRV can be considered effective in monitoring altitude effects on autonomic control of cardiac rhythms, when direct or more effective measures (such as microneurography) are harsh to implement.…”

Acute Moderate Hypoxia Reduces One-Legged Cycling Performance Despite Compensatory Increase in Peak Cardiac Output: A Pilot Study

“…Although this result appears to be influenced by a single subject displaying a large increase in MABP, it seems intriguing to speculate that baroreceptor activity might be involved in the regulation of CO in acute moderate hypoxia ( Figure 2 ). Baroreflex sensitivity (hypocapnia triggered) is usually reduced in acute hypoxia, potentially related to an insufficient CO elevation to compensate for the hypoxia-related loss in VO 2peak [ 18 , 19 ]. A sufficient CO increase was particularly prevented in individuals with higher (but normal) values of systemic BP (and BP changes from normoxia to hypoxia), likely due to enhanced baroreceptor activity and the associated reduction in sympathetic activation and cardiac output [ 20 ].…”