Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin-aldosterone system (RAAS) is a hormonal system that has a critical role in maintaining the normotensive state and electrolyte balance of the organism. The RAAS also has an important influence in the development of various pathophysiological conditions especially those concerning the renal system, cardiovascular system and hypertension. One of the consequences of the RAAS system is an increase in the generation of the reactive oxygen species (ROS) that causes an increase in oxidative stress, which may play a role in the development or exacerbation of such pathological conditions. Blocking this system at multiple points has been advantageous in the clinical management of these disorders. The key blockers that had gained predominant clinical use for such manifestations were angiotensin receptor blockers and angiotensin-converting enzyme (ACE) inhibitors. However, their prolonged use caused a compensatory increase in renin and angiotensin I levels. The blocking of the system at the initial stages by blocking renin was of advantage to overcome such compensation. Such a renin blocker that gained widespread use was aliskiren. It is the first oral renin inhibitor that was approved for use in 2007. Although the opinions are varied about the use and future of renin inhibitors as antihypertensive agents, aliskiren has been well documented to have antioxidant effects. Aliskiren functions as an antioxidant by lowering the increase in ROS that are produced by the RAAS system at doses independent of decreasing the blood pressure. In the present review we discuss the antioxidant properties of aliskiren independent of its blood pressure lowering property.
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PMID:Aliskiren - A promising antioxidant agent beyond hypertension reduction. 3248 50

Atrial fibrillation (AF) is frequently associated with increased inflammatory response characterized by infiltration of monocytes/macrophages. The chemokine receptor CXCR-2 is a critical regulator of monocyte mobilization in hypertension and cardiac remodeling, but it is not known whether CXCR-2 is involved in the development of hypertensive AF. AF was induced by infusion of Ang II (angiotensin II; 2000 ng/kg per minute) for 3 weeks in male C57BL/6 wild-type mice, CXCR-2 knockout mice, bone marrow-reconstituted chimeric mice, and mice treated with the CXCR-2 inhibitor SB225002. Microarray analysis revealed that 4 chemokine ligands of CXCR-2 were significantly upregulated in the atria during 3 weeks of Ang II infusion. CXCR-2 expression and the number of CXCR2+ immune cells markedly increased in Ang II-infused atria in a time-dependent manner. Moreover, Ang II-infused wild-type mice had increased blood pressure, AF inducibility, atrial diameter, fibrosis, infiltration of macrophages, and superoxide production compared with saline-treated wild-type mice, whereas these effects were significantly attenuated in CXCR-2 knockout mice and wild-type mice transplanted with CXCR-2-deficient bone marrow cells or treated with SB225002. Moreover, circulating blood CXCL-1 levels and CXCR2+ monocyte counts were higher and associated with AF in human patients (n=31) compared with sinus rhythm controls (n=31). In summary, this study identified a novel role for CXCR-2 in driving monocyte infiltration of the atria, which accelerates atrial remodeling and AF after hypertension. Blocking CXCR-2 activation may serve as a new therapeutic strategy for AF.
Hypertension 2020 Aug
PMID:Chemokine Receptor CXCR-2 Initiates Atrial Fibrillation by Triggering Monocyte Mobilization in Mice. 3263 81

Dysfunctions of vascular smooth muscle cells (VSMCs) play crucial roles in vascular remodeling in hypertension, which correlates with pathologically elevated cyclic stretch due to increased arterial pressure. Recent researches reported that autophagy, a life-sustaining process, was increased in hypertension. However, the mechanobiological mechanism of VSMC autophagy and its potential roles in vascular remodeling are still unclear. Using renal hypertensive rats in vivo and FX5000 stretch application Unit in vitro, the autophagy of VSMCs was detected. The results showed that LC3II remarkably enhanced in hypertensive rats and 15% cyclic stretch (mimic the pathologically increased mechanical stretch in hypertension), and the activity of mammalian target of rapamycin (mTOR) was suppressed in 15% cyclic stretch. Administration of autophagy inhibitors, bafilomycin A1 and chloroquine, repressed VSMC proliferation efficiently, but did not affect the degradation of two important nuclear envelope (NE) proteins, lamin A/C and emerin. Using RNA interference to decline the expression of lamin A/C and emerin, respectively, we discovered that autophagy was upregulated under both static and 5% cyclic stretch conditions, accompanying with the decreased mTOR activity. During 15% cyclic stretch application, mTOR inhibition was responsible for autophagy elevation. Chloroquine administration in vivo inhibited the expression of PCNA (marker of proliferation) of abdominal aorta in hypertensive rats. Altogether, these results demonstrated that pathological cyclic stretch suppresses the expression of lamin A/C and emerin which subsequently represses mTOR pathway so as to induce autophagy activation. Blocking autophagic flux may be a practicable way to relieve the pathological vascular remodeling in hypertensive.
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PMID:Suppressed nuclear envelope proteins activate autophagy of vascular smooth muscle cells during cyclic stretch application. 3292 41

Day by day, the health and economical burden of cancer increases globally. Indeed it can be considered that there is ''cancer pandemic''. Blocking the renin-angiotensin system (RAS) by angiotensin-converting enzyme (ACE) inhibitors (ACEI) or angiotensin-receptor blockers (ARB) are widely used measures to treat hypertension and heart failure. It has been recently suggested the activation and blocking of RAS has been associated with various types of cancer in epidemiological and experimental studies. Various studies have shown that RAS blockage is protective in some cancers. However, although fewer, contradictory data also showed that RAS blockage is either not related or adversely related to cancer. Although the reasons for these findings are not exactly known, different types of receptors and effectors in RAS may account for these findings. In the current review, we summarize the different RAS receptors and cancer development with regard to epidemiology, and pathogenesis including cell signaling pathways, apoptosis, genetic and epigenetic factors.
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PMID:Renin-angiotensin system and cancer: epidemiology, cell signaling, genetics and epigenetics. 3293 Sep 20


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