1,721,040 research outputs found
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
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
Endothelin-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
Vascular actions of insulin with implications for endothelial dysfunction
No full textHemodynamic actions of insulin depend largely on the hormone’s ability to stimulate
synthesis and release of endothelial mediators, whose balanced activity ensures
dynamic control of vascular function. Nitric oxide (NO), endothelin-1 (ET-1), and
reactive oxygen species (ROS) are important examples of endothelial mediators
with opposing properties on vascular tone, hemostatic processes, and vascular
permeability. Reduced NO bioavailability, resulting from either insufficient production
or increased degradation of NO, characterizes endothelial dysfunction. In
turn, endothelial dysfunction predicts vascular complications of metabolic and
hemodynamic disorders. In the cardiovascular system, insulin stimulates the production
and release of NO, ET-1, and ROS via activation of distinct intracellular
signaling pathways. Under insulin-resistant conditions, increased insulin concentrations
and/or impaired insulin-signaling pathways in the vasculature may contribute
to imbalance in secretion of endothelial mediators that promote pathogenesis
of vascular abnormalities. This short review describes signaling pathways involved
in insulin-stimulated release of NO, ROS, and ET-1 and suggests possible molecular
mechanisms by which abnormal insulin signaling may contribute to endothelial
dysfunction
Determinants of evolving cardiovascular benefit/risk profile of rosiglitazone during the natural hystory of diabetes
No full textRosiglitazone is a thiazolidinedione (TZD), a synthetic PPARγ receptor agonist with insulin-sensitizing properties that is used as an anti-diabetic drug. In addition to improving glycemic control through actions in metabolic target tissues, rosiglitazone has numerous biological actions that impact on cardiovascular homeostasis. Some of these actions are helpful (e.g., improving endothelial function) while others are potentially harmful (e.g., promoting fluid retention). Since cardiovascular morbidity and mortality are major endpoints for diabetes, it is essential to understand how the natural history of diabetes alters the net benefits and risks of rosiglitazone therapy. This complex issue is an important determinant of optimal use of rosiglitazone and is critical for understanding cardiovascular safety issues. We give special attention to the effects of rosiglitazone in diabetic patients with stable coronary artery disease (CAD) and the impact of rosiglitazone actions on atherosclerosis and plaque instability. This provides a rational conceptual framework for predicting evolving benefit/risk profiles that inform optimal use of rosiglitazone in the clinical setting and help explaining results of recent large clinical intervention trials where rosiglitazone had disappointing cardiovascular outcomes. Thus, in this review, we describe what is known about the molecular mechanisms of action of rosiglitazone on cardiovascular targets in the context of the evolving pathophysiology of diabetes over its natural history
Cardiovascular Complications in Diabetes: Lessons from Animal Models
No full textMicro- and macro-vascular complications are the leading causes of morbidity and mortality in type 1 and type 2 diabetic patients. Despite the vast clinical experience linking diabetic metabolic abnormalities to cardiovascular lesions, the molecular basis of individual susceptibility to diabetic cardiovascular injury is still largely unknown. Significant advances in this area may come from studies on suitable animal models. Although no animal model can accurately reproduce the human disease, experimental studies in animals have the great advantage to eliminate factors such as ethnicity, economic and geographic variables, drug interactions, diet, gender and age differences that importantly limit clinical studies. Indeed, appropriate animal models have provided important information on genetic and environmental risks of diabetes, and helped to dissect molecular mechanisms underlying the development, progression and therapeutic control of this disease. Unfortunately, none of the diabetic models presently available fully mimics the human syndrome. Therefore, the current knowledge on the pathogenesis of cardiovascular complications relies on the evaluation of distinct phenotypes from various diabetic models. In addition to strains prone to diabetes, this disease can be induced by surgical, pharmacological or genetic manipulation in several animal species. Rodents are the most used, although some studies are still performed in larger animals as rabbits, cats, pigs or monkeys. Far from being exhaustive, this work should serve as a general overview of the most relevant clues provided by major species and models for the overall comprehension of cardiovascular complications in type 1 and type 2 diabetes
INCREASED P22PHOX EXPRESSION AND REDUCED SOD ACTIVITY ARE INVOLVED IN EARLY IMPAIRMENT OF INSULIN-INDUCED VASODILATION ON RESISTANCE VESSELS OF SPONTANEOUSLY HYPERTENSIVE RATS (SHR)
No full textImmunoregulatory effects of L-arginine and therapeutical implications
No full textArginine, initially classified as a non-essential amino acid, participates to multiple biological processes including release of several hormones, collagen synthesis during wound healing, antitumor and antibacterial activities and non-specific immunity. Nitric oxide synthase and arginase competes for L-arginine as a substrate and this event appears to play a key role in the regulation of the inflammatory process. In this framework recent studies have identified complex patterns of interactions among these enzymes. This review will emphasizes some effects of L-arginine on immune cell functions, including triggering of L-arginine-nitric oxide and arginase pathways, its biological properties and therapeutical applications
The Intrinsic Virtues of EGCG, an Extremely Good Cell Guardian, on Prevention and Treatment of Diabesity Complications
Full text linkThe pandemic proportion of diabesity-a combination of obesity and diabetes-sets a worldwide health issue. Experimental and clinical studies have progressively reinforced the pioneering epidemiological observation of an inverse relationship between consumption of polyphenol-rich nutraceutical agents and mortality from cardiovascular and metabolic diseases. With chemical identification of epigallocatechin-3-gallate (EGCG) as the most abundant catechin of green tea, a number of cellular and molecular mechanisms underlying the activities of this unique catechin have been proposed. Favorable effects of EGCG have been initially attributed to its scavenging effects on free radicals, inhibition of ROS-generating mechanisms and upregulation of antioxidant enzymes. Biologic actions of EGCG are concentration-dependent and under certain conditions EGCG may exert pro-oxidant activities, including generation of free radicals. The discovery of 67-kDa laminin as potential EGCG membrane target has broaden the likelihood that EGCG may function not only because of its highly reactive nature, but also via receptor-mediated activation of multiple signaling pathways involved in cell proliferation, angiogenesis and apoptosis. Finally, by acting as epigenetic modulator of DNA methylation and chromatin remodeling, EGCG may alter gene expression and modify miRNA activities. Despite unceasing research providing detailed insights, ECGC composite activities are still not completely understood. This review summarizes the most recent evidence on molecular mechanisms by which EGCG may activate signal transduction pathways, regulate transcription factors or promote epigenetic changes that may contribute to prevent pathologic processes involved in diabesity and its cardiovascular complications
The Connection Between Physical Exercise and Gut Microbiota: Implications for Competitive Sports Athletes
Full text linkGut microbiota refers to those microorganisms in the human digestive tract that display activities fundamental in human life. With at least 4 million different bacterial types, the gut microbiota is composed of bacteria that are present at levels sixfold greater than the total number of cells in the entire human body. Among its multiple functions, the microbiota helps promote the bioavailability of some nutrients and the metabolization of food, and protects the intestinal mucosa from the aggression of pathogenic microorganisms. Moreover, by stimulating the production of intestinal mediators able to reach the central nervous system (gut/brain axis), the gut microbiota participates in the modulation of human moods and behaviors. Several endogenous and exogenous factors can cause dysbiosis with important consequences on the composition and functions of the microbiota. Recent research underlines the importance of appropriate physical activity (such as sports), nutrition, and a healthy lifestyle to ensure the presence of a functional physiological microbiota working to maintain the health of the whole human organism. Indeed, in addition to bowel disturbances, variations in the qualitative and quantitative microbial composition of the gastrointestinal tract might have systemic negative effects. Here, we review recent studies on the effects of physical activity on gut microbiota with the aim of identifying potential mechanisms by which exercise could affect gut microbiota composition and function. Whether physical exercise of variable work intensity might reflect changes in intestinal health is analyzed
- …
