Epidermal growth factor receptor tyrosine kinase (EGFRtk) and endoplasmic reticulum (ER) stress are important factors in cardiovascular complications. Understanding whether enhanced EGFRtk activity ER induction involved cardiac damage, microvascular dysfunction type 1 diabetes mellitus is an question that has remained unanswered. Cardiac fibrosis function were determined C57BL/6J mice injected with streptozotocin only or combination inhibitor (AG1478), (Tudca), insulin for 2 weeks. In...

Type 2 diabetes (T2D) is associated with vascular dysfunction. We hypothesized that increased nuclear factor-κB (NF-κB) signaling contributes to dysfunction in T2D. treated type diabetic (db(-)/db(-)) and control (db(-)/db(+)) mice two NF-κB inhibitors (6 mg/kg dehydroxymethylepoxyquinomicin twice a week 500 μg/kg/day IKK-NBD peptide) for 4 weeks. Pressure-induced myogenic tone was significantly potentiated, while endothelium-dependent relaxation (EDR) impaired small coronary arterioles...

Abstract Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of cardiovascular complications. However, and mechanisms ER hypertension remain unclear. Thus, we hypothesized that enhanced contributes maintenance spontaneously hypertensive rats (SHRs). Sixteen-week old male SHRs Wistar Kyoto Rats (WKYs) were used this study. The treated with inhibitor (Tauroursodeoxycholic acid; TUDCA, 100 mg/kg/day) for two weeks. There was decrease systolic blood...

Aims Mechanogated ion channels are predicted to mediate pressure-induced myogenic vasoconstriction in small resistance arteries. Recent findings have indicated that transient receptor potential (TRP) and epithelial sodium (ENaC) involved mechanotransduction. The purpose of this study was investigate the role TRP ENaC response. Our previous suggested could be a component mechanosensitive rat posterior cerebral arteries (PCA). However, specific channel proteins mediating constriction unknown....

Compound C is an adenosine monophosphate‑activated protein kinase (AMPK) inhibitor, which also recognized as a broad‑spectrum inhibitor with anti‑proliferative effects. The present study investigated the therapeutic effects of high concentration compound on Graves' orbitopathy (GO) pathogenesis beyond AMPK‑dependent pathway using human orbital fibroblasts. Orbital connective tissue was obtained from patients GO and healthy controls, primary fibroblasts were cultured. cells then pretreated...

Endoplasmic reticulum (ER) stress and inflammation are important mechanisms that underlie many of the serious consequences type II diabetes. However, role ER in impaired ischaemia-induced neovascularization diabetes is unknown. We studied hind-limb 4-week-old db - /db- mice their controls treated with or without inhibitor (tauroursodeoxycholic acid, TUDCA, 150 mg/kg per day) interleukin-1 receptor antagonist (anakinra, 0.5 µg/mouse for 4 weeks. Blood pressure was similar all groups mice....

Type 2 diabetes mellitus (T2DM) is associated with microvascular dysfunction. We hypothesized that increased poly(ADP-ribose) polymerase 1 (PARP-1) activity contributes to dysfunction in T2DM. T2DM (db − /db ) and nondiabetic control + mice were treated different PARP-1 inhibitors (INO-1001, 5 mg/kg per day ABT-888, 15 day) for weeks. Isolated coronary arterioles mounted an arteriograph. Pressure-induced myogenic tone was significantly potentiated, whereas endothelium-dependent relaxation...

What is the central question of this study? Endoplasmic reticulum (ER) stress has been reported to be involved in type 2 diabetes; however, role exacerbated ER vascular dysfunction diabetes remains unknown. main finding and its importance? The findings study are that increased coronary arteries diabetes, inhibition using taurine-conjugated ursodeoxycholic acid improves function, which associated with normalization myogenic response endothelium-dependent relaxation. Vascular a major...

Mutations in the serine-threonine kinase with-no-lysine 4 (WNK4) cause pseudohypoaldosteronism type 2 (PHAII), a Mendelian form of human hypertension. WNK4 regulates diverse ion transporters kidney, and dysregulation renal is considered main mutation-associated Another determinant hypertension vascular tone that regulated by Ca 2+ -dependent blood vessel constriction. However, role vasoconstriction as part its function to regulate pressure not known. Here, we report unique modulator...

Type 2 diabetes is associated with vascular complication. We hypothesized that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox expression impairs endothelium-dependent relaxation (EDR) in type diabetes. diabetic ( db − /db ) and control + mice were treated reactive oxygen species (ROS) scavenger, polyethylene glycol superoxide dismutase (1,000 U/kg daily ip), or small interfering RNA (p22 -lentivirus-small RNA, 100 μg iv, times/wk) for 1 mo. EDR was...

Although stimulation with sphingosylphosphorylcholine (SPC) or sphingosine-1-phosphate (S1P) generally leads to similar vascular responses, the contractile patterns and their underlying signalling mechanisms are often distinct. We investigated different reliance upon Ca2+-dependent Ca2+-sensitizing of constriction in response SPC S1P coronary arteries. Contractile changes [Ca2+]i, phosphorylation myosin light chain phosphatase-targeting subunit (MYPT1) were measured. induced a...

The goal of the current study was to determine whether sphingosine kinase 1 (SK1)/sphingosine-1-phosphate (S1P) pathway is involved in myogenic vasoconstriction under normal physiological conditions. In present study, we assessed endogenous S1P generated by pressure participates and which signaling pathways are SK1/S1P-induced response conditions.We measured pressure-induced response, Ca(2+) concentration, 20 kDa myosin light chain phosphorylation (MLC(20)) rabbit posterior cerebral arteries...

Type 2 diabetes is a key risk factor for ischemia-dependent pathology; therefore, significant medical need exists to develop novel therapies that increase the formation of new vessels. We explored therapeutic potential epidermal growth receptor tyrosine kinase (EGFRtk) and extracellular signal–regulated 1/2 (ERK1/2) inhibition in impaired ischemia-induced neovascularization type diabetes. Unilateral femoral artery ligation was performed diabetic (db−/db−) their control (db−/db+) mice 4...

Background/Aims Although polypoid leiomyomas in the colon and rectum are rare, they increasingly detected during colonoscopy. The aim of this study was to evaluate efficacy clinical outcomes endoscopic removal for colorectal leiomyoma. Methods Data were retrospectively collected from 22 patients with leiomyoma arising muscularis mucosae who underwent at single referral gastrointestinal endoscopy unit. Colonoscopic findings, removal, success rates, complication rates (bleeding or...

What is the central question of this study? role autophagy in vascular dysfunction type 2 diabetes? main finding and its importance? Autophagy decreased mesenteric arteries diabetic mice, stimulation using rapamycin trehalose improves function, which associated with normalization myogenic response endothelium-dependent relaxation.Vascular a major complication diabetes (T2D). It has been suggested that dysregulation various cardiovascular diseases. However, relationship between T2D remains...

We investigated if the magnitude of myogenic tone in basilar artery SHR differs from that WKY and, so, whether RhoA- or PKC-dependent mechanisms were involved. Myogenic was developed response to stretch. Stretch-induced contraction significantly greater than presence external Ca<sup>2+</sup>. However, absence Ca<sup>2+</sup>, stretch did not evoke a tone. The [Ca<sup>2+</sup>]<sub>i</sub>-induced larger and...

The effects of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), an inhibitor the activation soluble guanylate cyclase (sGC) on responses to NO donors acetylcholine (ACh) and bradykinin (BK) were investigated in pulmonary systemic vascular beds rat. In these studies administration ODQ a dose 5 mg/kg iv attenuated vasodilator five different without inhibiting ACh BK Vasodilator not inhibited by l-NAME or transient receptor vanilloid type 4 (TRPV4) antagonist GSK-2193874, which TRPV4 agonist...

Abstract Hypertension is characterized by increased peripheral vascular resistance which related with elevated myogenic response. Recent findings have indicated that epithelial sodium channel (ENaC) involved in mechanotransduction of the The purpose this study was to investigate involvement ENaC response posterior cerebral arteries (PCAs) from spontaneously hypertensive rats (SHRs). Sixteen eighteen weeks old male wistar kyoto (WKYs) and SHRs were used study. We found wall lumen (W/L) ratio...