Hydrogen sulfide-mediated cardioprotection: mechanisms and therapeutic potential

H2S (hydrogen sulfide), viewed with dread for more than 300 years, is rapidly becoming a ubiquitously present and physiologically relevant signalling molecule. Knowledge of the production and metabolism of H2S has spurred interest in delineating its functions both in physiology and pathophysiology of disease. Although its role in blood pressure regulation and interaction with NO is controversial, H2S, through its anti-apoptotic, anti-inflammatory and antioxidant effects, has demonstrated significant cardioprotection. As a result, a number of sulfide-donor drugs, including garlic-derived polysulfides, are currently being designed and investigated for the treatment of cardiovascular conditions, specifically myocardial ischaemic disease. However, huge gaps remain in our knowledge about this gasotransmitter. Only by additional studies will we understand more about the role of this intriguing molecule in the treatment of cardiovascular disease.

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Anti-Hypertensive Potential and Epigenetics of Angiotensin II type 2 Receptor (AT2R)

Current Hypertension Reviews ◽

10.2174/1573402116999201209203015 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mayank Chaudhary

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Renin Angiotensin System ◽

Blood Pressure Regulation ◽

Biologically Active ◽

Pressure Regulation ◽

Tissue Remodelling ◽

Critical Pathway

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.

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Evaluation of thionolactones as a new type of hydrogen sulfide (H2S) donors for a blood pressure regulation

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104650 ◽

2021 ◽

Vol 108 ◽

pp. 104650

Author(s):

Ewelina Zaorska ◽

Marta Gawryś-Kopczyńska ◽

Ryszard Ostaszewski ◽

Marcin Ufnal ◽

Dominik Koszelewski

Keyword(s):

Blood Pressure ◽

Hydrogen Sulfide ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

New Type

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Sex- and age-based differences in the effect of central serotonin on arterial blood pressure regulation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00414.2020 ◽

2020 ◽

Vol 129 (6) ◽

pp. 1310-1323

Author(s):

Jennifer L. Magnusson ◽

Craig A. Emter ◽

Kevin J. Cummings

Keyword(s):

Blood Pressure ◽

Arterial Blood Pressure ◽

Nrem Sleep ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Adult Rats ◽

Arterial Blood ◽

Serotonin Neurons ◽

Older Males

The role of serotonin in arterial blood pressure (ABP) regulation across states of vigilance is unknown. We hypothesized that adult rats devoid of CNS serotonin (TPH2−/−) have low ABP in wakefulness and NREM sleep, when serotonin neurons are active. However, TPH2−/− rats experience higher ABP than TPH2+/+ rats in wakefulness and REM only, a phenotype present only in older males and not females. CNS serotonin may be critical for preventing high ABP in males with aging.

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[BP.10.03] DETERMINING THE ROLE OF FIBRE, THROUGH CHANGES IN THE GUT MICROBIOTA, IN BLOOD PRESSURE REGULATION

Journal of Hypertension ◽

10.1097/01.hjh.0000524023.02886.ac ◽

2017 ◽

Vol 35 ◽

pp. e345-e346

Author(s):

F. Marques ◽

A. Fiedler ◽

D. Horlock ◽

C. Mackay ◽

D. Kaye

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Blood Pressure Regulation ◽

Pressure Regulation

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Blood pressure regulation by ETA and ETB receptors in conscious, telemetry-instrumented mice and role of ETA in hypertension produced by selective ETB blockade

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01221.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. H2554-H2559 ◽

Cited By ~ 14

Author(s):

Ryan M. Fryer ◽

Pamela A. Rakestraw ◽

Patricia N. Banfor ◽

Bryan F. Cox ◽

Terry J. Opgenorth ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Blood Pressure Regulation ◽

Pressure Regulation ◽

Type B ◽

Selective Antagonist ◽

Relevant Role ◽

Basal Blood Pressure ◽

Baseline Values

The net contribution of endothelin type A (ETA) and type B (ETB) receptors in blood pressure regulation in humans and experimental animals, including the conscious mouse, remains undefined. Thus we assessed the role of ETA and ETB receptors in the control of basal blood pressure and also the role of ETA receptors in maintaining the hypertensive effects of systemic ETB blockade in telemetry-instrumented mice. Mean arterial pressure (MAP) and heart rate were recorded continuously from the carotid artery and daily (24 h) values determined. At baseline, MAP ranged from 99 ± 1 to 101 ± 1 mmHg and heart rate ranged between 547 ± 15 and 567 ± 19 beats/min ( n = 6). Daily oral administration of the ETB selective antagonist A-192621 [10 mg/kg twice daily] increased MAP to 108 ± 1 and 112 ± 2 mmHg on days 1 and 5, respectively. Subsequent coadministration of the ETA selective antagonist atrasentan (5 mg/kg twice daily) in conjunction with A-192621 (10 mg/kg twice daily) decreased MAP to baseline values on day 6 (99 ± 2 mmHg) and to below baseline on day 8 (89 ± 3 mmHg). In a separate group of mice ( n = 6) in which the treatment was reversed, systemic blockade of ETB receptors produced no hypertension in animals pretreated with atrasentan, underscoring the importance of ETA receptors to maintain the hypertension produced by ETB blockade. In a third group of mice ( n = 10), ETA blockade alone (atrasentan; 5 mg/kg twice daily) produced an immediate and sustained decrease in MAP to values below baseline (baseline values = 101 ± 2 to 103 ± 2 mmHg; atrasentan decreased pressure to 95 ± 2 mmHg). Thus these data suggest that ETA and ETB receptors play a physiologically relevant role in the regulation of basal blood pressure in normal, conscious mice. Furthermore, systemic ETB receptor blockade produces sustained hypertension in conscious telemetry-instrumented mice that is absent in mice pretreated with an ETA antagonist, suggesting that ETA receptors maintain the hypertension produced by ETB blockade.

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