1,721,113 research outputs found
Diabetic cardiomyopathy: how much does it depend on AGE?
No full textDiabetic cardiomyopathy refers to dysfunction of cardiac muscle in patients with diabetes that cannot be directly ascribed to
hypertension, coronary heart disease or other defined cardiac abnormalities per se. The development of diabetic
cardiomyopathy may involve several distinct mechanisms, including increased formation of advanced glycation end
products (AGEs) secondary to hyperglycaemia. AGEs may alter structural proteins and lead to increased arterial and myocardial
stiffness. Therefore, therapies that prevent or retard development of AGEs in diabetes may be valuable strategies to treat or
prevent diabetic cardiomyopathy. In this issue of British Journal of Pharmacology, Wu and colleagues demonstrate that
aminoguanidine (inhibitor of AGE formation and protein cross-linking) treatment of a rat model of type I diabetes (rats made
insulin deficient with streptozotocin and nicotinamide treatment) ameliorates detrimental changes in left ventricular structure
and function. Results from this study are in agreement with previous investigations, suggesting that aminoguanidine is
effective in preventing cardiac hypertrophy and arterial stiffening in experimental animal models of diabetes and emphasize
the potential pathogenic role of AGEs in diabetic cardiomyopathy
In vivo and in vitro effects of epigallocatechin gallate on intestinal motility of spontaneously hypertensive rats
No full textIN VIVO AND IN VITRO EFFECTS OF EPIGALLOCATECHIN GALLATE (EGCG) ON INTESTINAL MOTILITY OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR)
POTENZA Maria Assunta, NACCI Carmela, MONTAGNANI Monica and DE SALVIA Maria Antonietta.
Dept. Biomedical Sciences and Human Oncology, Medical School, University of Bari, Piazza G. Cesare, 70124 Bari, Italy
Anti-hypertensive effects of green tea drinking are mediated by its most abundant catechin, EGCG. EGCG reaches the highest concentrations in the intestine, where it reduces lipids absorption, inhibits angiogenesis and decreases cancer cell proliferation. Whether EGCG may interfere with gastrointestinal motility is not known. The present study investigates the effects of EGCG on intestinal motility of SHR and WKY rats. For in vivo studies, 9-wk old male SHR were administered with EGCG (200 mg/kg/day) or vehicle (n = 5/group) by gavage for 3 weeks. The contractile dose-response to carbachol (0.05 – 5 μM) and the inhibitory response to electrical field stimulation (EFS, 1- 10 Hz, 13 V, 1 msec, 10-sec train duration) from colon and duodenum specimens were measured before and after L-NNA (100 μM), and compared between EGCG- and vehicle-treated SHR. Colonic response to carbachol and duodenal response to L-NNA were respectively reduced and increased (p < 0.05) in EGCG-treated SHR (vs. vehicle). For in vitro studies, the contractile response to carbachol (1.5 μM) and the inhibitory response to EFS (5 Hz) were measured in colonic and duodenal specimens before and after EGCG (100 μM), and results in SHR compared to those obtained in WKY. EGCG significantly reduced colonic response to carbachol only in SHR, whereas a decreased duodenal inhibitory response to EFS (5 Hz) after EGCG was observed in both SHR and WKY. These data suggest that EGCG may influence intestinal motility, and that gastrointestinal side effects might be associated with drinking of green tea, particularly in hypertensive patients
Insulin action in vascular endothelium: potential mechanisms linking insulin resistance with hypertension RID B-1970-2008
No full textn
Abnormal Insulin Signaling: Early Detection of Silent Coronary Artery Disease-Erectile Dysfunction?
No full textCoronary Artery Disease (CAD) and erectile dysfunction (ED) are cardiovascular complications frequently occurring in patients with diabetes, obesity, and dyslipidemia. All these metabolic disorders are characterized by insulin resistance, defined as decreased sensitivity and/or responsiveness to metabolic actions of insulin promoting glucose disposal. Insulin resistance is not only a hallmark of metabolic abnormalities, but also a prominent feature of haemodynamic disorders. Indeed, insulin-stimulated release of endothelial factors takes part into the physiological regulation of vascular function, and altered insulin actions may profoundly affect cardiovascular homeostasis under metabolic derangement. The signpost of impaired vascular reactivity is endothelial dysfunction, a condition in which the endothelium loses its physiological ability to produce the vasodilator nitric oxide (NO). A number of molecular, cellular, physiological, and clinical studies have indicated that insulin resistance may impair NO release and damage endothelial function through several patho-physiological mechanisms reciprocally interconnected. Although considered the earliest marker of impaired vascular health, endothelial dysfunction is initially asymptomatic; additional changes in the vessel structure are usually required before vascular complications manifest. Nevertheless, endothelial dysfunction may become clinically evident when endothelial-mediated relaxation is necessary and sufficient to exert a specific effect. ED may be the first expression of endothelial dysfunction, and therefore represents a sentinel event in the clinical appearance of silent CAD. Thus, insulin resistance triggers endothelial dysfunction, and endothelial dysfunction may manifest as ED long before CAD or other vascular complications become clinically evident. This review briefly outlines the main characteristics of endothelial function and dysfunction, and describes the signaling pathways involved in cardiovascular actions of insulin under physiological and pathological conditions. Moreover, potential cellular and molecular mechanisms linking insulin resistance to early CAD-ED detection are also illustrated
Mitochondria and Reactive Oxygen Species
No full textFascination by the mitochondria, “the colonial posterity of
migrant prokaryocytes, probably primitive bacteria that
swam into ancestral precursors of our eukaryotic cells and
stayed there,”1 stems from the above-mentioned nebulous
endosymbiotic theory of their origin, as well as from the
growing realization of a very special role that they play in the
pathogenesis of diverse diseases.
These organelles generate energy primarily in the form of
the electrochemical proton gradient (H), which fuels
ATP production, ion transport, and metabolism.2 Generation
of this universal energy currency, H, occurs through the
series of oxidative reactions conducted by the respiratory
chain complexes at the ion-impermeable, almost cholesterolfree
inner membrane. Reduced nicotinamide adenine dinucleotide
represents the entry point to the complex I (reduced
nicotinamide adenine dinucleotide:ubiquinone reductase),
whereas the reduced ubiquinol enters the respiratory chain in
the complex III (ubiquinol:cytochrome c [cyt-c] reductase) to
reduce cyt-c, the electron carrier to the complex IV, cyt-c
oxidase. Each of these steps generates H by electrogenic
pumping of protons from the mitochondrial matrix to the
intermembrane space and is coupled to electron flow, thus
generating the electric membrane potential of 180 to 220
mV and a pH gradient of 0.4 to 0.6 U across the inner
mitochondrial membrane resulting in the negatively charged
matrix side of the membrane and alkaline matrix. Ultimately,
accumulated H is converted into the influx of protons
into the matrix driving ATP synthesis or protein transport. In
addition, these end points are necessary for the execution of
2 major enzymatic metabolic pathways within the mitochondrial
matrix: the tricarboxylic acid (TCA) oxidation cycle and
the fatty acid -oxidation pathway. This intricate system
fueling cellular functions is as elegant as it is vulnerable:
practically every component of the system, from the electron
transport chain complexes to the permeability properties of
the membranes, is a target for various noxious stimuli, some
of which can be generated within mitochondria themselves.
The list of these noxious stimuli is too long to be recounted
here, and the interested reader may refer to a recent excellent
review.3 These ancestral oxygen-using proteobacterial invaders
carried with them into eukaryotic cells not only evolutionary
benefits but also potential side reactions, most dangerous
of which are “exothermic oxygen combustion and free
radical emission.” This review is focused on one component
of the noxious mitochondrial pathway: reactive oxygen species
(ROS) from a mitochondrial perspective, which has
previously been extensively reviewed.4 Therefore, we shall
present the most recent findings but periodically offer historical
perspective
Insulin-stimulated activation of eNOS requires IRS-1 to couple signaling from the insulin receptor to PI 3-kinase pathways RID B-1970-2008
No full textEndothelin-1: The yin and yang on vascular function
No full textAbstract: Endothelin-1 (ET-1) is a vasoconstrictor secreted by endothelial cells, which acts as the natural
counterpart of the vasodilator nitric oxide (NO). ET-1 contributes to vascular tone and regulates cell
proliferation through activation of ETA and ETB receptors. Physical factors such as shear stress, or stimuli
including thrombin, epinephrine, angiotensin II, growth factors, cytokines and free radicals enhance secretion
of ET-1. By contrast, mediators like nitric oxide (NO), cyclic GMP, atrial natriuretic peptide, and prostacyclin
reduce the release of endogenous ET-1. Thus, under normal conditions, the effects of the ET-1 are carefully
regulated through inhibition or stimulation of ET-1 release from endothelium.
Endothelial dysfunction is one of the earliest landmarks of vascular abnormalities. Altered function of
endothelium may result from absolute decrease in bioavailability of NO as well as from relative augment in ET-
1 synthesis, release or activity. Imbalance in the production of vasodilator and vasoconstrictor agents may
contribute to the onset of hemodynamic disorders.
Since dysregulation of the endothelin system is important in the pathogenesis of several cardiovascular
diseases, the ETA and ETB receptors are attractive therapeutic targets for disorders associated with elevated ET-
1 levels. ET receptor antagonists may be regarded as disease-modifying agents thanks to their ability to
preserve endothelial integrity when the endothelin system is overactive.
This review summarizes the current knowledge on the role of ET-1 in experimental hypertension and describes
recent findings on the involvement of MAPK signalling pathways in ET-1 release in hypertension associated
with insulin resistance.
Moreover, therapeutic applications of ET-1 receptor blockers are also discussed
- …
