Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut and Neuroinflammation.

Background Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. We have demonstrated that OSA induces gut dysbiosis, and this dysbiotic microbiota contributes to hypertension. However, the mechanisms linking gut dysbiosis to blood pressure regulation remain unclear.

Alterations of the gut microbial community structure and function with aging in the spontaneously hypertensive stroke prone rat.

Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood-brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT.

Restructuring the Gut Microbiota by Intermittent Fasting Lowers Blood Pressure.

[Figure: see text].

The gut microbiome contributes to blood-brain barrier disruption in spontaneously hypertensive stroke prone rats.

In recent years, it has become apparent that the gut microbiome can influence the functioning and pathological states of organs and systems throughout the body. In this study, we tested the hypothesis that the gut microbiome has a major role in the disruption of the blood-brain barrier (BBB) in the spontaneously hypertensive stroke prone rats (SHRSP), an animal model for hypertensive cerebral small vessel disease (CSVD). Loss of BBB is thought to be an early and initiating component to the full expression of CSVD in animal models and humans.

Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance.

Aging is associated with cognitive decline and decreased concentrations of short-chain fatty acids (SCFAs) in the gut. SCFAs are significant in that they are protective to the gut and other organs. We tested the hypothesis that the aged gut microbiome alone is sufficient to decrease SCFAs in the host and produce cognitive decline.

Age-dependent involvement of gut mast cells and histamine in post-stroke inflammation.

Background: Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine.

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.

Rationale: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown.

Twik-2 mouse demonstrates pulmonary vascular heterogeneity in intracellular pathways for vasocontractility.

We have previously shown Twik-2 mice develop pulmonary hypertension and vascular remodeling. We hypothesized that distal pulmonary arteries (D-PAs) of the Twik-2 mice are hypercontractile under physiological venous conditions due to altered electrophysiologic properties between the conduit and resistance vessels in the pulmonary vascular bed. We measured resting membrane potential and intracellular calcium through Fura-2 in freshly digested pulmonary artery smooth muscles (PASMCs) from both the right main (RM-PA) and D-PA (distal) regions of pulmonary artery from WT and Twik-2 mice.

Prebiotics, Probiotics, and Acetate Supplementation Prevent Hypertension in a Model of Obstructive Sleep Apnea.

Disruption of the gut microbiota, termed gut dysbiosis, has been described in animal models of hypertension and hypertensive patients. We have shown that gut dysbiosis plays a causal role in the development of hypertension in a rat model of obstructive sleep apnea (OSA). Functional analysis of the dysbiotic microbiota in OSA demonstrates a loss of short chain fatty acid-producing bacteria.

Age-related changes in the gut microbiota influence systemic inflammation and stroke outcome.

Objective: Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in the gut microbiota, or dysbiosis, may be responsible for age-related inflammation.

Methods: Using stroke as a disease model, we tested the hypothesis that a youthful microbiota, when established in aged mice, produces positive outcomes following ischemic stroke.

Obstructive Sleep Apnea-Induced Hypertension: Role of the Gut Microbiota.

Purpose Of Review: Obstructive sleep apnea (OSA) is a significant risk factor for systemic hypertension and other cardiovascular diseases. While this relationship has been firmly established, a detailed understanding of how OSA leads to hypertension is lacking. This review will examine the emerging idea that the gut microbiota plays a role in the development of hypertension, including that associated with OSA.

Alterations in the gut microbiota can elicit hypertension in rats.

Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled.

The rat cerebral vasculature exhibits time-of-day-dependent oscillations in circadian clock genes and vascular function that are attenuated following obstructive sleep apnea.

Circadian clock components oscillate in cells of the cardiovascular system. Disruption of these oscillations has been observed in cardiovascular diseases. We hypothesized that obstructive sleep apnea, which is associated with cerebrovascular diseases, disrupts the cerebrovascular circadian clock and rhythms in vascular function.

Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.

Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA.

Pathological effects of obstructive apneas during the sleep cycle in an animal model of cerebral small vessel disease.

We tested the hypothesis that apneas during the sleep cycle exacerbate hypertension and accelerate changes that occur with cerebral small vessel disease. Obstructive sleep apnea was modeled by intermittent inflations of a chronically implanted tracheal balloon to occlude the airway during the sleep cycle (termed OSA) in spontaneously hypertensive stroke-prone (SHRSP) rats, a model of cerebral small vessel disease. SHRSP rats and their parent strain, Wistar Kyoto (WKY) rats, were exposed to OSA for 2 weeks (from 9 to 11 or from 18 to 20 weeks).

Increased cerebrovascular sensitivity to endothelin-1 in a rat model of obstructive sleep apnea: a role for endothelin receptor B.

Obstructive sleep apnea (OSA) is associated with cerebrovascular diseases. However, little is known regarding the effects of OSA on the cerebrovascular wall. We tested the hypothesis that OSA augments endothelin-1 (ET-1) constrictions of cerebral arteries.

A new rodent model for obstructive sleep apnea: effects on ATP-mediated dilations in cerebral arteries.

Obstructive sleep apnea (OSA), a condition in which the upper airway collapses during sleep, is strongly associated with metabolic and cardiovascular diseases. Little is known how OSA affects the cerebral circulation. The goals of this study were 1) to develop a rat model of chronic OSA that involved apnea and 2) to test the hypothesis that 4 wk of apneas during the sleep cycle alters endothelium-mediated dilations in middle cerebral arteries (MCAs).