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Interaction between angiotensin and endothelin

Radko Komers, Horacio Plotkin
Inhibition of the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in treatment of chronic kidney diseases (CKD). However, reversal of the course of CKD or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. New treatments are needed to enhance protective actions of RAAS inhibitors (RAASis), such as angiotensin-converting enzyme (ACE) inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), and improve prognosis in CKD patients...
May 15, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Denise C Cornelius, Javier Castillo, Justin Porter, Lorena M Amaral, Nathan Campbell, Adrienne Paige, Alexia J Thomas, Ashlyn Harmon, Mark W Cunningham, Kedra Wallace, Florian Herse, Gerd Wallukat, Ralf Dechend, Babbette LaMarca
Preeclampsia (PE) is associated with altered immune activation during pregnancy. We have previously shown that adoptive transfer of CD4(+) T cells from the reduced uterine perfusion pressure (RUPP) rat model of PE increases blood pressure, oxidative stress (ROS), and inflammation in normal pregnant recipient rats. The objective of this study was to determine if blockade of communication via the CD40-CD40 ligand (CD40L) interaction between placental ischemia-induced CD4(+) T cells with endogenous normal pregnant (NP) cells would improve pathophysiology that was previously observed in NP recipient rats of RUPP CD4(+) T cells...
November 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A Deshpande, Steven S An, Stephen B Liggett
Asthma is characterized by airway inflammation and airflow obstruction from human airway smooth muscle (HASM) constriction due to increased local bronchoconstrictive substances. We have recently found bitter taste receptors (TAS2Rs) on HASM, which increase [Ca2+]i and relax the muscle. We report here that some, but not all, TAS2R agonists decrease [Ca2+]i and relax HASM contracted by G-protein coupled receptors (GPCRs) that stimulate [Ca2+]i. This suggests both a second pathway by which TAS2Rs relax, and, a heterogeneity of the response phenotype...
2015: PloS One
Branislava Ivanovic, Marijana Tadic
The aim of this review article is to summarize the current knowledge about mechanisms that connect blood pressure regulation and hypercholesterolemia, the mutual interaction between hypertension and hypercholesterolemia, and their influence on atherosclerosis development. Our research shows that at least one-third of the population of Western Europe has hypertension and hypercholesterolemia. Several biohumoral mechanisms could explain the relationship between hypertension and hypercholesterolemia and the association between these risk factors and accelerated atherosclerosis...
December 2015: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
Jessica Bolaños, Luis Fernando De León, Edgardo Ochoa, José Darias, Huzefa A Raja, Carol A Shearer, Andrew N Miller, Patrick Vanderheyden, Andrea Porras-Alfaro, Catherina Caballero-George
Fungi occupy an important ecological niche in the marine environment, and marine fungi possess an immense biotechnological potential. This study documents the fungal diversity associated with 39 species of sponges and determines their potential to produce secondary metabolites capable of interacting with mammalian G-protein-coupled receptors involved in blood pressure regulation. Total genomic DNA was extracted from 563 representative fungal strains obtained from marine sponges collected by SCUBA from the Caribbean and the Pacific regions of Panama...
October 2015: Marine Biotechnology
D Walter Wray, Russell S Richardson
What is the topic of this review? This review focuses on age-related changes in the regulatory pathways that exist at the unique interface between the vascular smooth muscle and the endothelium of the skeletal muscle vasculature, and how these changes contribute to impairments in exercising skeletal muscle blood flow in the elderly. What advances does it highlight? Several recent in vivo human studies from our group and others are highlighted that have examined age-related changes in nitric oxide, endothelin-1, alpha adrenergic, and renin-angiotensin-aldosterone (RAAS) signaling...
June 2015: Experimental Physiology
Jamal Ahmad
Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD) affecting ∼20-30% diabetics, is associated with increased cardiovascular mortality. The progression of kidney disease in patients with diabetes can take many years. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Hyperglycaemia, hypertension, and genetic pre-disposition are the main risk factors besides elevated serum lipids, smoking habits, and the amount of dietary proteins...
October 2015: Diabetes & Metabolic Syndrome
Marcelo S Vatta, Liliana G Bianciotti, María J Guil, Sandra I Hope
Neuronal norepinephrine (NE) uptake is a crucial step in noradrenergic neurotransmission that regulates NE concentration in the synaptic cleft. It is a key mechanism mediated by the NE transporter (NET) which takes the neurotransmitter into the presynaptic neuron terminal or the adrenal medulla chromaffin cell. The activity of NET is short and long terms modulated by phosphorylation mediated by protein kinases A, C, and G and calcium-calmodulin-dependent protein kinase, whereas the transporter availability at the cell surface is regulated by glycosylation...
2015: Vitamins and Hormones
Karina Thieme, Maria Oliveira-Souza
The role of hyperleptinemia in cardiovascular diseases is well known; however, in the renal tissue, the exact site of leptin's action has not been established. This study was conducted to assess the effect of leptin treatment for 7 and 28 days on renal function and morphology and the participation of angiotensin II (Ang II), through its AT1 receptor. Rats were divided into four groups: sham, losartan (10 mg/kg/day, s.c.), leptin (0.5 mg/kg/day for the 7 days group and 0.25 mg/kg/day for the 28 days group) and leptin plus losartan...
2015: PloS One
Xinyu Weng, Liming Yu, Peng Liang, Luyang Li, Xin Dai, Bisheng Zhou, Xiaoyan Wu, Huihui Xu, Mingming Fang, Qi Chen, Yong Xu
Angiotensin II (Ang II) induces cardiac hypertrophy and fibrosis in part by stimulating endothelin (ET-1) transcription. The involvement of the epigenetic machinery in this process is largely undefined. In the present study, we examined the epigenetic maneuvering underlying cardiac hypertrophy and fibrosis following ET-1 transactivation by Ang II. In response to Ang II stimulation, core components of the mammalian chromatin remodeling complex (Brahma-related gene 1, or Brg1, and Brahma or Brm) and histone H3K4 methylation complex (Ash2, absent, small, or homeotic discs 2, or Ash2 and WD domain repeat 5, or Wdr5) were recruited to the ET-1 promoter region in endothelial cells...
May 2015: Journal of Molecular and Cellular Cardiology
Juergen Konczalla, Stefan Wanderer, Jan Mrosek, Patrick Schuss, Johannes Platz, Erdem Güresir, Volker Seifert, Hartmut Vatter
Investigations have shown a multifactorial process as cause for the poor outcome after subarachnoid hemorrhage (SAH), including inflammation, early brain injury, cortical spreading depression, lack of cerebral autoregulation and the cerebral vasospasm (CVS) itself. Losartan may have a beneficial effect after SAH - preventing CVS, restoring cerebral autoregulation, reducing inflammation and early brain injury. Also some data is available for an AT1-receptor-upregulation and upregulated gene expression after subarachnoid hemorrhage, but the functional role of angiotensin on the cerebrovascular contractility is still not completely understood...
November 2013: Current Neurovascular Research
Hongliang Zhang, Yamin Li, Yan Zeng, Renrong Wu, Jianjun Ou
BACKGROUND/AIMS: Both endothelin-1 (ET-1) and the renin-angiotensin system (RAS) are implicated in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). In the present study, we explored the interaction between ET-1 and the RAS by examining the effect of ET-1 on angiotensin-converting enzyme-2 (ACE2) expression and activity in human bronchial epithelial cells (HBEpCs). METHODS: HBEpCs were treated with ET-1 (1, 10, 20, 40 or 50 nmol/l) for 6, 12, 18, 24 or 30 h with or without the transcription inhibitor actinomycin D, endothelin A (ETA) receptor blocker BQ123, endothelin B receptor blocker BQ788, or different kinase inhibitors...
2013: Pharmacology
Dusko Kardum, Damir Fabijanić, Anita Lukić, Zeljko Romić, Mladen Petrovecki, Zoran Bogdanović, Klara Jurić, Marija Urek-Crncević, Marko Banić
Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30)...
June 2012: Collegium Antropologicum
J Zicha, Z Dobešová, M Vokurková, H Rauchová, S Hojná, M Kadlecová, M Behuliak, I Vaněčková, J Kuneš
Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension - salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P. Rapp has published the first and so far the only comprehensive review on this rat model covering numerous aspects of pathophysiology and genetics of salt hypertension. When we summarized 25 years of our own research on Dahl/Rapp rats, we have realized the need to outline principal abnormalities of this model, to show their interactions at different levels of the organism and to highlight the ontogenetic aspects of salt hypertension development...
2012: Physiological Research
Hong Xue, Li Zhou, Ping Yuan, Zhen Wang, Jun Ni, Tai Yao, Jun Wang, Yu Huang, Chen Yu, Limin Lu
In the updated concept of renin-angiotensin system (RAS), it contains the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-angtiogensin type 1 receptor (AT1) axis and the angiotensin-converting enzyme-related carboxypeptidase (ACE2)-Ang-(1-7)-Mas axis. The former axis has been well demonstrated performing the vasoconstrictive, proliferative and pro-inflammatory functions by activation of AT1 receptors, while the later new identified axis is considered counterbalancing the effects of the former. The present study is aimed at observing the interaction between Ang-(1-7) and Ang II on cultured rat renal mesangial cells (MCs)...
August 20, 2012: Regulatory Peptides
Tanja Ouimet, Eric Lancelot, Fabien Hyafil, Mario Rienzo, François Deux, Marjorie Lemaître, Sophie Duquesnoy, Jérome Garot, Bernard P Roques, Jean-Baptiste Michel, Claire Corot, Sébastien Ballet
P947 (DOTA-Gd-peptide) was recently identified as an MRI contrast agent for the detection and characterization of the matrix metalloproteinases (MMP)-rich atherosclerotic plaques. Because this product displays a broad spectrum affinity for the MMP family, we hypothesized that it may also recognize other metalloproteinases overactivated in vulnerable atherosclerotic plaques. Therefore, this study aimed at describing, at the molecular and cellular level, the interactions between P947 and proteases of atherosclerotic plaques...
April 2, 2012: Molecular Pharmaceutics
Yi-chi Zhang, Yan-ling Mou, Yan-ying Xie
Renin-angiotensin system (RAS) is activated in diabetes. The rise of angiotension II (Ang II) stimulates the cardiac fibroblast proliferation and the alteration of collagen metabolism through AT1 receptor on cell surface, causing the myocardium interstitial and perivascular fibrosis, and the ventricular myocardium rigidity and diastolic function disturbance, leading to the clinical symptoms of diabetic cardiomyopathy (DCM). The main members of RAS including Ang II, Ang-(1-7), Ac-SDKP and ATR play the important role in the development of DCM...
August 2011: Sheng Li Ke Xue Jin Zhan [Progress in Physiology]
Julio Scharfstein, Daniele Andrade
Acting at the interface between microcirculation and immunity, Trypanosoma cruzi induces modifications in peripheral tissues which translate into mutual benefits to host/parasite balance. In this chapter, we will review evidence linking infection-associated vasculopathy to the proinflammatory activity of a small subset of T. cruzi molecules, namely GPI-linked mucins, cysteine proteases (cruzipain), surface glycoproteins of the trans-sialidase family and/or parasite-derived eicosanoids (thromboxane A(2)). Initial insight into pathogenesis came from research in animal models showing that myocardial fibrosis is worsened as result of endothelin upregulation by infected cardiovascular cells...
2011: Advances in Parasitology
Claudia Grossmann, Michael Gekle
The mineralocorticoid receptor (MR) is a steroid receptor that physiologically regulates water and electrolyte homeostasis but that can also induce pathophysiological effects in the renocardiovascular system. Classically, the MR acts as a transcription factor at glucocorticoid response elements but additional protein-protein interactions with other signaling cascades have been described. Of these, the crosstalk with EGFR signaling is especially interesting because various vasoactive substances like angiotensin II and endothelin-1 also mediate their pathophysiological effects via the EGFR...
March 24, 2012: Molecular and Cellular Endocrinology
Martin Houde, Julie Labonté, Pedro D'Orléans-Juste
As for other peptides such as bradykinin, neurokinins and angiotensins, peptide antagonists for endothelin-1 (ET-1) have been early on developed towards the pharmacological characterization of both ET(A) and ET(B) receptors. Interestingly, unlike the previously mentioned three peptides, receptors for ET-1 were cloned and purified prior to the report of ET(A)and ET(B)receptor antagonists such as BQ-123 and BQ-788. The availability of such pharmacological tools and the use of molecular approaches have certainly fast-tracked the development of non-peptide ET receptor antagonists for clinical applications...
2011: Current Pharmaceutical Design
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