Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is a pleiotropic hormone produced primarily by the endothelium. Synthesis of ET-1 is stimulated by the major signals of cardiovascular stress, such as vasoactive agents (angiotensin II, norepinephrine, vasopressin, and bradykinin), cytokines (e.g., tumor necrosis factor alpha and transforming growth factor beta), and other factors, including thrombin and mechanical stress. ET-1 induces vasoconstriction, is proinflammatory, promotes fibrosis, and has mitogenic potential, important factors in the regulation of vascular tone, arterial remodeling, and vascular injury. These effects are mediated via two receptor types, ETA and ETB. The role ET-1 plays in normal cardiovascular homeostasis and in mild essential hypertension in humans is unclear. However, certain groups of essential hypertensive patients may have ET-1-dependent hypertension, including blacks (subjects of African descent), salt-sensitive hypertensives, patients with low renin hypertension, and those with obesity and insulin resistance. ET-1 has also been implicated in severe hypertension, heart failure, atherosclerosis, and pulmonary hypertension. In all of these conditions, plasma immunoreactive ET levels are elevated and tissue ET-1 expression is increased. Accordingly, it is becoming increasingly apparent that ET-1 plays an important role in cardiovascular disease and in some forms of hypertension in humans. Data from clinical trials using combined ETA-ETB receptor blockers have already demonstrated significant blood-pressure-lowering effects. Thus, targeting the endothelin system may have important therapeutic potential in the treatment of hypertension, particularly by contributing to the prevention of target organ damage and the management of cardiovascular disease.
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PMID:Role of endothelin in human hypertension. 1283 65

1. The present study explored the impact of endothelin (ET) and its interaction with renal sympathetic nerves in the control of volume homeostasis in obesity. 2. Groups of lean and obese Zucker rats with innervated and denervated kidneys were subjected to an acute isotonic saline volume expansion (VE), 10% bodyweight and renal haemodynamics and excretory function were evaluated following administration of SB209670 (a non-selective ET antagonist) or UK 350 926 (a selective ETA receptor antagonist). 3. Volume expansion in untreated obese rats resulted in a blunted cumulative urine sodium excretion (CuUNaV) after 40 min, VE compared with untreated lean rats being 36 and 51% in the denervated and innervated kidneys, respectively (both P < 0.001). 4. In lean rats, both SB209670 and UK 350 926 caused a depressed ability to excrete the saline load and CuUNaV after 40 min, VE compared with untreated being decreased by 51 and 60% in the denervated and innervated kidneys, respectively (both P < 0.001). 5. SB209670 and UK 350 926 given to obese rats reduced (both P < 0.001) CuUNaV after VE by 43% in denervated kidneys compared with untreated obese rats, whereas they were without effect on the magnitude of the excretory response in innervated kidneys. 6. These findings show that the blunted renal excretory responses to VE present in obese rats were not mediated by ET. Conversely, ET, acting through ETA receptors, plays a role as a diuretic and natriuretic factor in maintaining volume homeostasis by, at least in lean rats, renal nerve-independent mechanisms.
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PMID:Significance of endothelin on volume homeostasis in obese Zucker rats. 1294 Aug 91

Hypertensive patients have increased endothelin-1-dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses (plethysmography) to intra-arterial infusion of an ETA receptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI > or =30 kg/m2; P<0.001) and overweight (BMI, 27 to 29.9 kg/m2; P=0.04) but not in lean (BMI <27 kg/m2; P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ETA blockade was observed in hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11; P=0.58). In human hypertension, increased BMI is associated with enhanced ETA-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients.
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PMID:Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. 1465 51

The diabetic heart shows increased fibrosis, which impairs cardiac function. Endothelin (ET)-1 and nuclear factor-kappaB (NF-kappaB) interactively regulate fibroblast growth. We have recently demonstrated that Punica granatum flower (PGF), a Unani anti-diabetic medicine, is a dual activator of peroxisome proliferator-activated receptor (PPAR)-alpha and -gamma, and improves hyperglycemia, hyperlipidemia, and fatty heart in Zucker diabetic fatty (ZDF) rat, a genetic animal model of type 2 diabetes and obesity. Here, we demonstrated that six-week treatment with PGF extract (500 mg/kg, p.o.) in Zucker diabetic fatty rats reduced the ratios of van Gieson-stained interstitial collagen deposit area to total left ventricular area and perivascular collagen deposit areas to coronary artery media area in the heart. This was accompanied by suppression of overexpressed cardiac fibronectin and collagen I and III mRNAs. Punica granatum flower extract reduced the up-regulated cardiac mRNA expression of ET-1, ETA, inhibitor-kappaBbeta and c-jun, and normalized the down-regulated mRNA expression of inhibitor-kappaBalpha in Zucker diabetic fatty rats. In vitro, Punica granatum flower extract and its components oleanolic acid, ursolic acid, and gallic acid inhibited lipopolysaccharide-induced NF-kappaB activation in macrophages. Our findings indicate that Punica granatum flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats, at least in part, by modulating cardiac ET-1 and NF-kappaB signaling.
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PMID:Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. 1630 13