HS-Eluting Hydrogels Promote In Vitro Angiogenesis and Augment In Vivo Ischemic Wound Revascularization.

Ischemic wounds are frequently encountered in clinical practice and may be related to ischemia secondary to diabetes, peripheral artery disease and other chronic conditions. Angiogenesis is critical to the resolution of ischemia. Hydrogen sulfide (HS) is now recognized as an important factor in this process.

Characterization of Mild Delayed Gestational Hypertension in Rats Following Ozone Exposure.

The contribution of air pollution induced cardio-pulmonary damage on the development of hypertensive disorders of pregnancy and other adverse outcomes of pregnancy has gained increased attention as epidemiological data continues to highlight spatiotemporal pregnancy trends related to air pollution exposure. However clinical mechanistic data surrounding gestational complications remains sparse, necessitating the need for the use of animal models to study these types of complications of pregnancy. The current study seeks to examine the real-time effects of mid-gestational ozone exposure on maternal blood pressure and body temperature through the use of radiotelemetry in a rat model.

A novel, microvascular evaluation method and device for early diagnosis of peripheral artery disease and chronic limb-threatening ischemia in individuals with diabetes.

Objective: A novel transdermal arterial gasotransmitter sensor (TAGS) has been tested as a diagnostic tool for lower limb microvascular disease in individuals with and without diabetes mellitus (DM).

Methods: The TAGS system noninvasively measures hydrogen sulfide (HS) emitted from the skin. Measurements were made on the forearm and lower limbs of individuals from three cohorts, including subjects with DM and chronic limb-threatening ischemia, to evaluate skin microvascular integrity.

Single-cell transcriptomic heterogeneity between conduit and resistance mesenteric arteries in rats.

The endothelium contains morphologically similar cells throughout the vasculature, but individual cells along the length of a single vascular tree or in different regional circulations function dissimilarly. When observations made in large arteries are extrapolated to explain the function of endothelial cells (ECs) in the resistance vasculature, only a fraction of these observations are consistent between artery sizes. To what extent endothelial (EC) and vascular smooth muscle cells (VSMCs) from different arteriolar segments of the same tissue differ phenotypically at the single-cell level remains unknown.

Hydrogen sulfide and miR21 are suitable biomarkers of hypoxic exposure.

Hypoxia is the reduction of alveolar partial pressure of oxygen ([Formula: see text]). Military members and people who practice recreational activities from moderate to high altitudes are at risk for hypoxic exposure. Hypoxemia's signs and symptoms vary from asymptomatic to severe responses, such as excessive hypoxic ventilatory responses and residual neurobehavioral impairment.

Role of Cholesterol in the Regulation of Hydrogen Sulfide Signaling within the Vascular Endothelium.

HS is a gaseous signaling molecule enzymatically produced in mammals and HS-producing enzymes are expressed throughout the vascular wall. We previously reported that HS-induced vasodilation is mediated through transient receptor potential cation channel subfamily V member 4 (TRPV4) and large conductance (BK) potassium channels; however, regulators of this pathway have not been defined. Previous reports have shown that membrane cholesterol limits activity of TRPV4 and BK potassium channels.

Hydrogen Sulfide Actions in the Vasculature.

Hydrogen sulfide (H S) is a small, gaseous molecule with poor solubility in water that is generated by multiple pathways in many species including humans. It acts as a signaling molecule in many tissues with both beneficial and pathological effects. This article discusses its many actions in the vascular system and the growing evidence of its role to regulate vascular tone, angiogenesis, endothelial barrier function, redox, and inflammation.

Guidelines for the measurement of vascular function and structure in isolated arteries and veins.

The measurement of vascular function in isolated vessels has revealed important insights into the structural, functional, and biomechanical features of the normal and diseased cardiovascular system and has provided a molecular understanding of the cells that constitutes arteries and veins and their interaction. Further, this approach has allowed the discovery of vital pharmacological treatments for cardiovascular diseases. However, the expansion of the vascular physiology field has also brought new concerns over scientific rigor and reproducibility.

Simulated sleep apnea alters hydrogen sulfide regulation of blood flow and pressure.

In sleep apnea, airway obstruction causes intermittent hypoxia (IH). In animal studies, IH-dependent hypertension is associated with loss of vasodilator hydrogen sulfide (HS), and increased HS activation of sympathetic nervous system (SNS) activity in the carotid body. We previously reported that inhibiting cystathionine γ-lyase (CSE) to prevent HS synthesis augments vascular resistance in control rats.

Portal Venous Flow Is Increased by Jejunal but Not Colonic Hydrogen Sulfide in a Nitric Oxide-Dependent Fashion in Rats.

Hydrogen sulfide (HS) is a recently discerned endogenous signaling molecule that modulates the vascular system. Endogenous hydrogen sulfide has been shown to dilate both the mesenteric and portal vasculature. Gut microbiome, via sulfur reducing bacteria, is another source of HS production within the gut lumen; this source of HS is primarily produced and detoxified in the colon under physiologic conditions.

Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling.

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCβ and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCβ mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoK), and stimulated production of mitoROS.

Hydrogen sulfide regulation of renal and mesenteric blood flow.

Hydrogen sulfide (HS) dilates isolated arteries, and knockout of the HS-synthesizing enzyme cystathionine γ-lyase (CSE) increases blood pressure. However, the contributions of endogenously produced HS to blood flow regulation in specific vascular beds are unknown. Published studies in isolated arteries show that CSE production of HS influences vascular tone more in small mesenteric arteries than in renal arteries or the aorta.

A dual blocker of endothelin A/B receptors mitigates hypertension but not renal dysfunction in a rat model of chronic kidney disease and sleep apnea.

Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse during sleep, resulting in intermittent hypoxia (IH), and is associated with a high incidence of hypertension and accelerated renal failure. In rodents, endothelin (ET)-1 contributes to IH-induced hypertension, and ET-1 levels inversely correlate with glomerular filtration rate in patients with end-stage chronic kidney disease (CKD). Therefore, we hypothesized that a dual ET receptor antagonist, macitentan (Actelion Pharmaceuticals), will attenuate and reverse hypertension and renal dysfunction in a rat model of combined IH and CKD.

Intermittent hypoxia exacerbates increased blood pressure in rats with chronic kidney disease.

Kidney injury and sleep apnea (SA) are independent risk factors for hypertension. Exposing rats to intermittent hypoxia (IH) to simulate SA increases blood pressure whereas adenine feeding causes persistent kidney damage to model chronic kidney disease (CKD). We hypothesized that exposing CKD rats to IH would exacerbate the development of hypertension and renal failure.

Vascular biology of hydrogen sulfide.

Hydrogen sulfide (HS) is a ubiquitous signaling molecule with important functions in many mammalian organs and systems. Observations in the 1990s ascribed physiological actions to HS in the nervous system, proposing that this gasotransmitter acts as a neuromodulator. Soon after that, the vasodilating properties of HS were demonstrated.

NFAT regulation of cystathionine γ-lyase expression in endothelial cells is impaired in rats exposed to intermittent hypoxia.

Sleep apnea is a risk factor for cardiovascular disease, and intermittent hypoxia (IH, 20 episodes/h of 5% O-5% CO for 7 h/day) to mimic sleep apnea increases blood pressure and impairs hydrogen sulfide (HS)-induced vasodilation in rats. The enzyme that produces HS, cystathionine γ-lyase (CSE), is decreased in rat mesenteric artery endothelial cells (EC) following in vivo IH exposure. In silico analysis identified putative nuclear factor of activated T cell (NFAT) binding sites in the CSE promoter.

Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels.

Hydrogen sulfide (HS) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous HS production and are required for HS-induced dilation. However, the signal transduction pathway activated by HS within EC has not been elucidated.

Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries.

Ca(+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and promote vasodilation by activating large-conductance Ca(2+)-activated potassium channels and inhibiting myogenic tone. We have previously reported that exposing rats to intermittent hypoxia (IH) to simulate sleep apnea augments myogenic tone in mesenteric arteries through loss of hydrogen sulfide (H2S)-induced dilation. Because we also observed that H2S can increase Ca(2+) spark activity, we hypothesized that loss of H2S after IH exposure reduces Ca(2+) spark activity and that blocking Ca(2+) spark generation reduces H2S-induced dilation.

Modulation of hydrogen sulfide by vascular hypoxia.

Hydrogen sulfide (HS) has emerged as a key regulator of cardiovascular function. This gasotransmitter is produced in the vasculature and is involved in numerous processes that promote vascular homeostasis, including vasodilation and endothelial cell proliferation. Although HS plays a role under physiological conditions, it has become clear in recent years that hypoxia modulates the production and action of HS.