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Hypertension is regulated by immunological components. Spontaneously hypertensive rats (SHR) display a large population of proinflammatory CD161 + immune cells. We investigated the effect of early post-natal gut microbiota on the development of the immune system and resulting hypertension in the SHR. We first examined the microbial populations in the fecal samples of SHR and normotensive control WKY using 16S rDNA sequencing. We found that in the newborn SHR (1-week old) the gut microbiota was qualitatively and quantitatively different from the newborns of normotensive WKY. The representation of the predominant bacterial phylum Proteobacteria was significantly less in 1-week old SHR pups than in WKY (94.5% Proteobacteria in WKY vs. 65.2% in SHR neonates). Even within the phylum Proteobacteria, the colonizing genera in WKY and SHR differed dramatically. Whereas WKY microbiota was predominantly comprised of Escherichia-Shigella, SHR microbiota was represented by other taxa of Enterobacteriaceae and Pasteurellaceae. In contrast, the representation of phylum Firmicutes in the neonatal SHR gut was greater than WKY. Cross-fostering newborn SHR pups by lactating WKY dams caused a dramatic shift in 1-week old cross-fostered SHR gut microbiota. The two major bacterial taxa of phylum Proteobacteria, Enterobacteriaceae and Pasteurellaceae as well as Lactobacillus intestinalis, Proteus, Romboustia and Rothia were depleted after cross-fostering and were replaced by the predominant genera of WKY (Escherichia-Shigella). A proinflammatory IL-17F producing CD161 + immune cell population in the spleen and aorta of cross-fostered SHR was also reduced (30.7% in self-fostered SHR vs. 12.6% in cross-fostered SHR at 30 weeks of age) as was the systolic blood pressure in adult cross-fostered SHR at 10 weeks of age. Thus, altered composition of gut microbiota of SHR toward WKY at early neonatal age had a long-lasting effect on immune system by reducing proinflammatory immune cells and lowering systolic blood pressure.

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Startle habituation is a type of implicit and automatic emotion regulation. Diminished startle habituation is linked to several psychiatric or neurological disorders. Most previous studies quantified startle habituation by assessing skin conductance response, eye-blink reflex, or motor response. The habituation of parasympathetic-mediated heart rate responses to recurrent startle stimuli is not well understood. A variety of methods and metrics have been used to quantify parasympathetic activity and its effects on the heart. We hypothesized that these different measures reflect unique psychological and physiological processes therefore may habituate differently during repeated startle stimuli. We measured cardiac inter-beat intervals (IBI) to recurring acoustic startle probes in 75 eight year old children. Eight acoustic stimuli of 500 ms duration were introduced at intervals of 15-25 seconds. Indices of parasympathetic effect included: 1) the initial rapid decrease in IBI post-startle mediated by parasympathetic inhibition; 2) the subsequent IBI recovery mediated by parasympathetic reactivation; 3) rapid, beat-to-beat heart rate variability measured from the first 7 IBIs following each startle probe. Skin conductance (reflecting sympathetic-mediated sweating) and motor responses to startles were also measured. Results showed that habituation of parasympathetic reactivation (IBI recovery and overshoot) and skin conductance responses were rapid and robust. In addition, changes in parasympathetic reactivation and skin conductance response were significantly correlated. In contrast, habituation of parasympathetic inhibition (the initial decrease in IBI) was slower and relatively modest. Measurement of rapid heart rate variability provided an index reflecting the combination of parasympathetic inhibition and reactivation. We conclude that different measures of parasympathetic activity habituate in a differential manner to repeated startle probes.

Chronic intermittent hypoxia (CIH) leads to increased sympathetic nerve activity and arterial hypertension. In this study, we tested the hypothesis that CIH impairs baroreflex (BR) control of heart rate (HR) in mice, and that decreased cardiac chronotropic responsiveness to vagal efferent activity contributes to such impairment. C57BL/6J mice were exposed to either room air (RA) or CIH (6-min alternations of 21% O2 and 5.7% O2, 12 h/day) for 90 days. After the treatment period, mice were anesthetized (Avertin) and arterial blood pressure (ABP) was measured from the femoral artery. Mean ABP (MABP) was significantly increased in mice exposed to CIH (98.7 ± 2.5 vs. RA: 78.9 ± 1.4 mmHg, P < 0.001). CIH increased HR significantly (584.7 ± 8.9 beats/min; RA: 518.2 ± 17.9 beats/min, P <0.05). Sustained infusion of phenylephrine (PE) at different doses (0.1-0.4 µg/min) significantly increased MABP in both CIH and RA mice, but the ABP-mediated decreases in HR were significantly attenuated in mice exposed to CIH (P <0.001). In contrast, decreases in HR in response to electrical stimulation of the left vagus nerve (30 µA, 2-ms pulses) were significantly enhanced in mice exposed to CIH compared with RA mice at low frequencies. We conclude that CIH elicits a sustained impairment of baroreflex control of HR in mice. The blunted BR-mediated bradycardia occurs despite enhanced cardiac chronotropic responsiveness to vagal efferent stimulation. This suggests that an afferent and/or a central defect is responsible for the baroreflex impairment following CIH. [ABSTRACT FROM AUTHOR]