Angiotensin II stimulates endothelin

BACKGROUND: Recent studies have shown that endothelin-1 and angiotensin II (AngII) can increase gap junctional intercellular communication (GJIC) by activating Mitogen-activated protein kinases (MAPKs) pathway. However, not only the precise interaction of AngII with Connexin43(Cx43) and the associated functions remain unclear, but also the regulatory role of Cx43 on the AngII-mediated promotion proliferation and migration of VSMCs is poorly understood. MATERIAL AND METHODS: Our research applicated pressure myography measurements, immunofluorescence and Western blot analyses to investigate the changes in physiological indicators in spontaneously hypertensive rats (SHRs) and AngII-stimulated proliferation and migration of A7r5 SMCs(Rat vascular smooth muscle cells)...

Picotamide is a thromboxane A2 (TXA2 ) receptor antagonist and TXA2 synthase inhibitor. In clinical studies, it has been considered as a platelet aggregation inhibitor and improved renal function. In vitro studies suggested inhibition of smooth muscle contraction by picotamide, which is poorly understood. Here, we examined effects of picotamide on contractions of renal interlobar and coronary porcine arteries, induced by different vasoconstrictors. Contractions were induced in an organ bath by agonists or electric field stimulation (EFS)...

The present study investigated the angiotensin II (Ang II) responses in rat femoral veins taken from 2-kidney-1clip (2K1C) hypertensive rats at 4 weeks after clipping, as well as the effects of exercise on these responses. In this manner, femoral veins taken from 2K1C rats kept at rest or exposed to acute exercise or to exercise training were challenged with Ang II or endothelin-1 (ET-1) in organ bath. Simultaneously, the presence of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were determined in these preparations by western blotting...

IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method...

OBJECTIVES: Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells...

BACKGROUND Hypertension could induce many serious diseases, including damage to vascular endothelial cells. As a non-coding RNA, long noncoding RNA (lncRNA) has received much attention in scientific research and has a regulating efficacy on many critical life activities in human body. The level of lncRNA AK094457 is thought to be elevated in hypertensive rats. However, there is no research indicating the relationship between the level of lncRNA AK094457 and vascular endothelial injury. MATERIAL AND METHODS In our study, we used lentiviral to knockdown lncRNA AK094457, and the human umbilical vein endothelial cells (HUVECs) were stimulated by the Ang II to imitate the vascular endothelial cell damage caused by hypertension...

Retrospective analyses and single-center prospective studies identify chronic metabolic acidosis as an independent and modifiable risk factor for progression of CKD. In patients with CKD, untreated chronic metabolic acidosis often leads to an accelerated reduction in GFR. Mechanisms responsible for this reduction include adaptive responses that increase acid excretion but lead to a decline in kidney function. Metabolic acidosis in CKD stimulates production of intrakidney paracrine hormones including angiotensin II, aldosterone, and endothelin-1 (ET-1) that mediate the immediate benefit of increased kidney acid excretion, but their chronic upregulation promotes inflammation and fibrosis...

Cost- and time-intensive porcine translational disease models offer great opportunities to test drugs and therapies for pathological cardiac hypertrophy and can be supported by porcine cell culture models that provide further insights into basic disease mechanisms. Cardiac progenitor cells (CPCs) residing in the adult heart have been shown to differentiate in vitro into cardiomyocytes and could contribute to cardiac regeneration. Therefore, it is important to evaluate their changes on the cellular level caused by disease...

BACKGROUND AND PURPOSE: The B-type natriuretic peptide (BNP1-32) exerts vasorelaxing and cardioprotective activity. BNP is used as a biomarker for the diagnosis of cardiopathological conditions and recombinant BNP1-32 as a drug for the treatment of such. BNP1-32 has a short half-life time and thus, similar to other vasoactive peptides like angiotensin II and bradykinin, can be enzymatically truncated forming bioactive metabolites. We aimed to investigate the metabolism of BNP1-32 in mouse lung, to identify potential new BNP metabolites and to disclose their biological activity compared to the BNP1-32, in vitro and in vivo...

Despite the availability of multiple antihypertensive drugs targeting the different pathways implicated in its pathophysiology, hypertension remains poorly controlled worldwide, and its prevalence is increasing because of the aging of the population and the obesity epidemic. Although nonadherence to treatment contributes to uncontrolled hypertension, it is likely that not all the pathophysiological mechanisms are neutralized by the various classes of antihypertensive treatment currently available, and, the counter-regulatory mechanisms triggered by these treatments may decrease their blood pressure-lowering effect...

Aim: Endothelin-1 (ET-1) and angiotensin II (Ang II) are multifunctional peptide hormones that regulate the function of the cardiovascular and renal systems. Both hormones increase the intracellular production of inositol-1,4,5-trisphosphate (IP3 ) by activating their membrane-bound receptors. We have previously demonstrated that IP3 -mediated sarcoplasmic reticulum (SR) Ca2+ release results in mitochondrial Ca2+ uptake and activation of ATP production. In this study, we tested the hypothesis that intact SR/mitochondria microdomains are required for metabolic IP3 -mediated SR/mitochondrial feedback in ventricular myocytes...

The present study was designed to elucidate the beneficial effects of XJEK on myocardial infarction (MI) in rats, especially through the amelioration of endothelial dysfunction (ED). 136 Sprague-Dawley rats were randomized into 13 groups: control group for 0wk ( n = 8); sham groups for 2, 4, and 6 weeks (wk); MI groups for 2, 4, and 6 wk; MI+XJEK groups for 2, 4, and 6w k; MI+Fosinopril groups for 2, 4, and 6 wk ( n = 8~10). In addition, 8 rats were treated for Evans blue staining and Tetrazolium chloride (TTC) staining to determine the infarct size...

Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot...

Previous studies have extensively demonstrated the effect of endothelin-1 (ET-1), angiotensin II (Ang II), and TGF-β1 on the stimulation of collagen type I expression in cardiac myofibroblasts. However, the role of pro-remodeling peptides in the transcriptional regulation of the collagen promoter remains unclear. Thus, the purpose of this study was to investigate the net regulatory effects of pro-remodeling peptides on collagen type I promoter activity. Constructs of various lengths (300 bp, 1.1 kbp, 1.7 kbp, 2...

AIMS: Hypertension is common. Recent data suggest that macrophages (Mφ) contribute to, and protect from, hypertension. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor with additional pro-inflammatory properties. We investigated the role of the ET system in experimental and clinical hypertension by modifying Mφ number and phenotype. METHODS AND RESULTS: In vitro, Mφ ET receptor function was explored using pharmacological, gene silencing, and knockout approaches...

Arterial hypertension is a disease with a complex pathogenesis. Despite considerable knowledge about this socially significant disease, the role of magnesium deficiency (MgD) as a risk factor is not fully understood. Magnesium is a natural calcium antagonist. It potentiates the production of local vasodilator mediators (prostacyclin and nitric oxide) and alters vascular responses to a variety of vasoactive substances (endothelin-1, angiotensin II, and catecholamines). MgD stimulates the production of aldosterone and potentiates vascular inflammatory response, while expression/activity of various antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and the levels of important antioxidants (vitamin C, vitamin E, and selenium) are decreased...

Cardiac hypertrophy, induced by neurohumoral factors, including angiotensin II and endothelin-1, is a major predisposing factor for heart failure. These ligands can induce hypertrophic growth of neonatal rat cardiomyocytes (NRCMs) mainly through Ca2+ -dependent calcineurin/nuclear factor of activated T cell (NFAT) signaling pathways activated by diacylglycerol-activated transient receptor potential canonical 3 and 6 (TRPC3/6) heteromultimer channels. Although extracellular nucleotide, adenosine 5'-triphosphate (ATP), is also known as most potent Ca2+ -mobilizing ligand that acts on purinergic receptors, ATP never induces cardiomyocyte hypertrophy...

KEY POINTS: We investigated the excitation-contraction coupling mechanisms in small pulmonary veins (SPVs) in rat precision-cut lung slices. We found that SPVs contract strongly and reversibly in response to extracellular ATP and other vasoconstrictors, including angiotensin-II and endothelin-1. ATP-induced vasoconstriction in SPVs was associated with the stimulation of purinergic P2Y2 receptors in vascular smooth muscle cell, activation of phospholipase C-β and the generation of intracellular Ca2+ oscillations mediated by cyclic Ca2+ release events via the inositol 1,4,5-trisphosphate receptor...

Women with preeclampsia produce AT1-AA (agonistic autoantibodies to the angiotensin II type 1 receptor), which stimulate reactive oxygen species, inflammatory factors, and hypertensive mechanisms (ET [endothelin] and sFlt-1 [soluble fms-like tyrosine kinase-1]) in rodent models of preeclampsia. The placental ischemic reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits many of these features. In this study, we examined the maternal outcomes of AT1-AA inhibition ('n7AAc') in RUPP rats...

Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2 /H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells that occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+ -dependent release of several neurotransmitters, some excitatory and others inhibitory, that help shape the afferent carotid sinus nerve (CSN) discharge...