• Hypertension
  • 1,2 AT 2 receptors are upregulated under conditions associated with cardiovascular tissue damage, such as myocardial infarction, heart failure, and hypertension. (ahajournals.org)
  • These findings may be applicable to the pathophysiology of renovascular hypertension, because aortic cGMP production was increased in 2-kidney, 1-clip Goldblatt hypertensive rats via activation of AT 2 receptors that stimulated endothelial NO synthase (eNOS) phosphorylation and NO production through a bradykinin B 2 receptor-dependent pathway. (ahajournals.org)
  • The excess white adipose tissue (WAT) that characterizes obesity is a major risk factor for the development of many diseases, such as diabetes, coronary heart disease, hypertension, stoke and some types of cancers (for example, colorectal cancer). (nature.com)
  • Therefore, deficits in AT 2 R expression may contribute to pregnancy-induced hypertension and thus represents a potential therapeutic target. (ahajournals.org)
  • CONCLUSIONS -ACEIs or ARBs may decrease patients' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality, cardiovascular, or cerebrovascular outcomes over the study follow-up periods among patients with hypertension. (thaiendocrine.org)
  • Which type of medication to use initially for hypertension has been the subject of several large studies and resulting national guidelines. (wikipedia.org)
  • It may also delay progression of diabetic nephropathy and is also indicated for the reduction of renal disease progression in patients with type 2 diabetes, hypertension and microalbuminuria (>30 mg/24 h) or proteinuria (>900 mg/24 h). (wikipedia.org)
  • stimulation
  • The number of TUNEL-positive nuclei was ≈0 to 10 per 100 000 cardiomyocytes, with no difference between transgenic and wild-type mice, regardless of saline infusion or any stimulation. (ahajournals.org)
  • 20 In the present study, we used these TG mice to examine whether AT 2 R stimulation enhances Ang II-induced cardiomyocyte apoptosis in vivo. (ahajournals.org)
  • Therefore, in the current study, we have examined the potential neuroprotective effect of AT 2 R stimulation initiated after stroke induction to mimic the clinical setting. (ahajournals.org)
  • Furthermore, we have demonstrated that AT 2 R stimulation after stroke increased neuronal survival, decreased apoptosis, and caused an increase in the number of activated microglia in the core region of damage. (ahajournals.org)
  • Thus, the current study has shown for the first time that delayed central AT 2 R stimulation after a cerebral incident is neuroprotective in a conscious rat model of stroke. (ahajournals.org)
  • Because AA and its metabolites are powerful modulators of neuronal K + currents, we investigated the involvement of PLA 2 and AA in the AT 2 receptor-mediated stimulation of I K by Ang II. (jneurosci.org)
  • Inhibition of lipoxygenase (LO) enzymes significantly reduced both Ang II- and AA-stimulated I K , and the 12-LO metabolite of AA 12 S -hydroxyeicosatetraenoic acid (12 S -HETE) stimulated I K . These data indicate the involvement of a PLA 2 , AA, and LO metabolite intracellular pathway in the AT 2 receptor-mediated stimulation of neuronal I K by Ang II. (jneurosci.org)
  • The data presented here indicate that the AT 2 receptor-mediated stimulation of neuronal I K by Ang II involves an intracellular pathway that includes PLA 2 , AA, and LO metabolites of AA. (jneurosci.org)
  • In addition, the results suggest that PP-2A may be important for the stimulation of neuronal I K produced by Ang II and AA. (jneurosci.org)
  • Angiotensin II, through AT1 receptor stimulation, is a major stress hormone and, because (ARBs) block these receptors, in addition to their eliciting anti-hypertensive effects, may be considered for the treatment of stress-related disorders. (wikipedia.org)
  • The activated receptor in turn couples to Gq/11 and thus activates phospholipase C and increases the cytosolic Ca2+ concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase and activates various tyrosine kinases. (wikipedia.org)
  • Thus, H 3 receptor-mediated NHE inhibition in ischemia/reperfusion not only opposes the angiotensin II-induced stimulation of NHE in cardiac sympathetic neurons, but also down-regulates AT 1 receptor expression. (aspetjournals.org)
  • The stimulation of the PVN by the activation of urotensin II receptor means that it directly affects the hypothalamus pituitary axis (HPA) which is important in the regulation of many important body functions. (wikipedia.org)
  • inhibition
  • An extreme way of cell growth inhibition directs cells into programmed cell death, and its process initiated by withdrawal of growth factors is also enhanced by AT2-R.Cardiac myocyte- or vascular smooth muscle-specific overexpression mice of AT2-R display an inhibitory effect on Ang II-induced chronotropic or pressor actions, suggesting the role of AT2-R on the activity of cardiac pacemaker cells or maintenance of vascular resistance. (nii.ac.jp)
  • This effect of Ang II was blocked by inhibition of phospholipase A 2 (PLA 2 ) and by PTX. (jneurosci.org)
  • Furthermore, the demonstration that inhibition of PP-2A abolished the stimulatory effects of Ang II, AA, and 12 S -HETE on neuronal I K but did not alter Ang II-stimulated [ 3 H]-AA release suggests that PP-2A is a distal event in this pathway. (jneurosci.org)
  • Pressor inhibition at trough level - this relates to the degree of blockade or inhibition of the blood pressure-raising ("pressor") effect of angiotensin II. (wikipedia.org)
  • NHE inhibition with cariporide prevented both increases in norepinephrine release and AT 1 receptor expression. (aspetjournals.org)
  • Effects mediated by the AT2 receptor are suggested to include inhibition of cell growth, fetal tissue development, modulation of extracellular matrix, neuronal regeneration, apoptosis, cellular differentiation, and maybe vasodilation and left ventricular hypertrophy. (wikipedia.org)
  • PD-123,319, commonly used in early angiotensin II research for its moderate inhibition of AT2R, blocks angiotensin II induced neuronal excitability in cultured cells of neuronal origins and also in cultured dorsal root ganglion neurons from adult rats. (wikipedia.org)
  • corticotropin-releas
  • When the urotensin II receptor is activated through an intracerebroventricular (icv) injection of urotensin II it causes an increase of corticotropin releasing factor through the activation of the hypothalamic paraventricular neurons (PVN) which lead to increased plasma levels of adrencorticotropic hormones. (wikipedia.org)
  • vasoconstriction
  • Ang II binding to AT 2 receptors activates a counterregulatory pathway whereby vasoconstriction mediated by AT 1 receptors is opposed by AT 2 receptor-induced vasodilation. (ahajournals.org)
  • Of importance, Ang II activation of AT 1 receptors was required for the upregulation of AT 2 receptors in the pressure-overloaded aorta, 19 suggesting the possibility of a counterregulatory positive feedback loop in which AT 1 receptor-mediated vasoconstriction is opposed by AT 1 receptor-induced AT 2 receptor upregulation, engendering counterregulatory vasodilation. (ahajournals.org)
  • The receptor quickly rose to prominence when it was found that when activated by urotensin II it induced the most potent vasoconstriction effect ever seen. (wikipedia.org)
  • Short term effects of the activation of the urotensin II receptor is the burst intercellular calcium in the aorta which causes vasoconstriction of the vessel. (wikipedia.org)
  • endothelial
  • We hypothesized that in the absence of endothelial NO synthase (eNOS), (1) left ventricular (LV) dysfunction and myocardial remodeling would be more severe after myocardial infarction (MI), and (2) the cardioprotective effect of ACEi and AT 1 -ant would be diminished or absent in mice with HF after MI. (ahajournals.org)
  • It is synthesized from l -arginine by the catalytic reaction of 3 different isoforms of NO synthase (NOS): neuronal or type 1 NOS (nNOS), inducible or type 2 NOS (iNOS), and endothelial or type 3 NOS (eNOS). (ahajournals.org)
  • neurons
  • 5 AT 2 R has been shown to mediate induction of apoptosis in the PC12 cell line, 6 vascular smooth muscle cells, 7 vascular endothelium, 8 fibroblasts, 9 granulose cells in the rat ovary, 10 neurons from the rat brain, 11 and human fetal adrenal cells. (ahajournals.org)
  • Angiotensin II (Ang II) elicits an Ang II type 2 (AT 2 ) receptor-mediated increase in delayed-rectifier K + current ( I K ) in neurons cultured from newborn rat hypothalamus and brainstem. (jneurosci.org)
  • On the other hand, when using in situ hybridization technique which is less sensitive but provides more information of the anatomical location urotensin II receptor mRNA was shown to be restricted to the brainstem cholinergic neurons of the laterodorsal tegmental (LDT) and the pedunculopontine tegmental nuclei (PPT) both of which are important for REM sleep. (wikipedia.org)
  • Urotensin II receptors are also found in the cholinergic neurons of the spinal cord indicating some type of motor function. (wikipedia.org)
  • Local injection of urotensin II into the PPT to leads to increased REM sleep episodes where the firing of the cholinergic neurons was observed through electrophysiological studies. (wikipedia.org)
  • vascular
  • 4,5 AT 2 receptor-mediated vasodilation has now been demonstrated in a large variety of resistance vessels including the mesenteric, uterine, renal, coronary, and cerebral vascular beds. (ahajournals.org)
  • We demonstrated that angiotensin II type 2 (AT 2 ) receptor-interacting protein (ATIP) 1 ameliorates inflammation-mediated vascular remodeling independent of the AT 2 receptor, leading us to explore the possibility of whether ATIP1 could exert anti-inflammatory effects and play a role in other pathophysiological conditions. (pubmedcentralcanada.ca)
  • The AT2 receptor remains enigmatic and controversial - is probably involved in vascular growth. (wikipedia.org)
  • pathway
  • Cathepsin F contains five potential N-glycosylation sites, and it may be targeted to the endosomal/lysosomal compartment via the mannose 6-phosphate receptor pathway. (wikipedia.org)
  • The receptor cannot activate the PKC but it can still activate the ERK1/2 pathway although it is a little bit slower. (wikipedia.org)
  • mice
  • Ten- to 12-week-old male homozygous transgenic mice (n=44) and wild-type mice (n=44) were used. (ahajournals.org)
  • It is unlikely that in mice the AT 2 receptor is a strong signal to induce cardiomyocyte apoptosis in vivo. (ahajournals.org)
  • We have recently developed transgenic (TG) mice overexpressing AT 2 R selectively in cardiomyocytes by using the α-myosin heavy chain promoter. (ahajournals.org)
  • TG mice overexpressing AT 2 R selectively in cardiomyocytes were generated using the α-myosin heavy chain promoter. (ahajournals.org)
  • Northern blot analysis of total RNA from various tissues of adult homozygous TG mice revealed that AT 2 R was exclusively and abundantly expressed in both atria and ventricles but not in other tissues. (ahajournals.org)
  • Mean arterial pressure was measured via telemetry, and flow cytometry was used to enumerate immune cell infiltration in 14-week-old wild-type and AT 2 R knockout mice during gestation. (ahajournals.org)
  • In wild-type mice, mean arterial pressure decreased during gestation, reaching a nadir at gestational day 9 (-6±2 mm Hg) and returned to near preconception levels during late gestation. (ahajournals.org)
  • In AT 2 R-deficient mice, the midgestational decrease in mean arterial pressure was absent. (ahajournals.org)
  • Furthermore, mean arterial pressure was significantly increased during late gestation compared with wild-type mice (≈10 mm Hg). (ahajournals.org)
  • However, this response was absent in AT 2 R-deficient mice. (ahajournals.org)
  • While renal immune cell infiltration was similar between the genotypes, there was a significant T cell phenotypic switch toward a proinflammatory T-helper 1 phenotype in AT 2 R-deficient mice. (ahajournals.org)
  • In mice fed a high-cholesterol diet, adipose tissue macrophage (ATM) infiltration and M1-to-M2 ratio were decreased in ATIP1 transgenic mice (ATIP1-Tg) compared with wild-type mice (WT), with decreased expression of inflammatory cytokines such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in white adipose tissue (WAT), but an increase in interleukin-10, an anti-inflammatory cytokine. (pubmedcentralcanada.ca)
  • Next, we examined the roles of ATIP1 in BM-derived hematopoietic cells, employing chimeric mice produced by BM transplantation into irradiated type 2 diabetic mice with obesity, KKAy, as recipients. (pubmedcentralcanada.ca)
  • eNOS knockout mice (eNOS−/−) and wild-type C57BL/6J (C57) mice (+/+) were subjected to MI by ligating the left coronary artery. (ahajournals.org)
  • blocker
  • METHODS: In this prospective, multicenter, double-blind, five-year study, we randomly assigned 250 subjects with type 2 diabetes and early nephropathy to receive either the angiotensin II-receptor blocker telmisartan (80 mg daily, in 120 subjects) or the ACE inhibitor enalapril (20 mg daily, in 130 subjects). (diva-portal.org)
  • Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes. (thaiendocrine.org)
  • In a study comparing beta-blocker carvedilol with valsartan, the angiotensin II receptor blocker not only had no deleterious effect on sexual function, but actually improved it. (wikipedia.org)
  • Structural modifications were made and the orally active, potent and selective nonpeptide AT1 receptor blocker losartan was developed. (wikipedia.org)
  • ligands
  • Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices. (wikipedia.org)
  • mRNA
  • Exons 1 and 2 encode for 5' untranslated mRNA sequence and exon 3 harbors the entire uninterrupted open reading frame. (wikipedia.org)
  • The protein's mRNA has been reported to interact with Mir-132 microRNA as part of an RNA silencing mechanism that reduces receptor expression. (wikipedia.org)
  • One is urotensin II whose mRNA is found in a variety of tissues including the brain and also blood vessels. (wikipedia.org)
  • AngII
  • Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. (nature.com)
  • Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. (clinsci.org)
  • In addition, our analysis in vitro using C 2 C 12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. (clinsci.org)
  • Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. (clinsci.org)
  • paracrine
  • Evidence has also accumulated, indicating that locally formed angiotensin II from the rat epididymis may play a paracrine and/or autocrine role in regulating epididymal electrolyte and fluid transport. (deepdyve.com)
  • The present finding of the differential patterns of angiotensin II receptor immunoreactivity in three different stages of the rat epididymis may reflect the fine tuning of rat epididymal function by angiotensin II, acting as a paracrine or autocrine agent, during the course of development. (deepdyve.com)
  • G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine, and endocrine processes). (wikipedia.org)
  • interacts
  • The transmembrane helices also contribute to the binding via the C-terminal carboxyl group that interacts with Lys199 in the upper part of helix 5 of the receptor, see figure 1 for details. (wikipedia.org)
  • Urotensin II Receptor interacts with the G Protein whose alpha subunit is Gαq11 which is mainly involved in activating Protein Kinase C (PKC). (wikipedia.org)
  • Losartan
  • Irbesartan and losartan have trial data showing benefit in hypertensive patients with type II diabetes,[citation needed] and may delay the progression of diabetic nephropathy. (wikipedia.org)
  • The specific AT1 affinity relates to how specifically attracted the medicine is for the correct receptor, the US FDA PI rates for AT1 affinity are as follows: Losartan 1000-fold Telmisartan 3000-fold Irbesartan 8500-fold Candesartan greater than 10000-fold Olmesartan 12500-fold Valsartan 30000-fold Saprisartan The third area needed to complete the overall efficacy picture of an ARB is its biological half-life. (wikipedia.org)
  • renin
  • It plays a role in the central nervous system and cardiovascular functions that are mediated by the renin-angiotensin system. (wikipedia.org)
  • In 1939, renin was found not to cause the rise in blood pressure, but was an enzyme which catalyzed the formation of the substances that were responsible, namely, angiotensin I (Ang I) and Ang II. (wikipedia.org)
  • In the 1970s, scientists first observed Ang II to harm the heart and kidneys, and individuals with high levels of renin activity in plasma were at increased risk of myocardial infarction and stroke. (wikipedia.org)