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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II is known to stimulate NADPH oxidase-dependent superoxide (O2-) generation, which may contribute to the acute renal vasoconstrictor and antinatriuretic actions of this peptide. To evaluate this hypothesis, the effects of a superoxide dismutase mimetic (tempol) or a NADPH inhibitor (apocynin) on the angiotensin renal actions were studied. Renal cortical nitric oxide (NO) was measured electrochemically in vivo. Tempol increased sodium excretion and NO levels. Apocynin raised renal blood flow, glomerular filtration rate, sodium excretion, and NO levels. These results indicate the presence of an endogenous NADPH oxidase-dependent O2- generation that may modulate renal function by scavenging NO. Angiotensin II infusion reduced renal blood flow, glomerular filtration, sodium excretion, and NO levels in a dose-dependent manner. The angiotensin receptor antagonist valsartan, tempol, or apocynin blunted the angiotensin effects on renal excretion and NO, suggesting that angiotensin receptors stimulation induces the NADPH oxidase-dependent O2- generation that might reduce NO bioavailability. This idea is supported by the finding that angiotensin increased O2- generation in renal homogenates, and this effect was prevented by valsartan, apocynin, or tempol. These results indicate that some of the acute renal effects of angiotensin II may be enhanced by an increased NADPH oxidase-derived O2- production that reduces renal NO bioavailability.
Hypertension 2003 Dec
PMID:Role of superoxide in modulating the renal effects of angiotensin II. 1459 45

1. Vascular cells have evolved to use reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, as signalling molecules. Under physiological conditions, ROS are important regulators of cell cycle, protein kinase activity and gene expression. However, in vascular disease states, such as hypertension and hypercholesterolaemia, excessive production of ROS may overwhelm the anti-oxidant defence mechanisms of cells, resulting in 'oxidative stress', damage to the artery wall and, ultimately, development of atherosclerotic plaques. 2. The primary source of ROS in the vasculature is NADPH oxidase. There appear to be at least three isoforms of NADPH oxidase expressed in the vascular wall, each differing with respect to the flavin-containing catalytic subunit it uses to transfer electrons from NADPH to molecular oxygen. Thus, although endothelial cells and adventitial fibroblasts express a gp91phox-containing NADPH oxidase similar to that originally identified in phagocytes, vascular smooth muscle cells may rely on novel homologues of gp91phox, namely Nox1 and Nox4, to produce superoxide. 3. Controversy remains over which isoform(s) of NADPH oxidase is responsible for the oxidative stress associated with vascular diseases. We and others have shown that although gp91phox mRNA expression is upregulated during atherogenesis in human and animal models, expression of the Nox4 subunit remains unchanged. Nox1 expression is also likely to be increased in diseased arteries; however, its relative level of expression, at least at the mRNA level, appears to be markedly lower than that of the other gp91phox homologues, even after upregulation. 4. Whether these findings suggest that a gp91phox-containing NADPH oxidase is more important than either Nox4 or Nox1 in vascular disease awaits studies examining relative protein expression and enzyme kinetics of each subunit, as well as the effects of targeted gene deletion of each of these gp91phox homologues on atherogenesis.
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PMID:Novel isoforms of NADPH oxidase in vascular physiology and pathophysiology. 1467 49

1. Reactive oxygen species (ROS) are a diverse family of molecules that are produced throughout the vascular wall. Many ROS, such as the superoxide anion (*O2-) and hydrogen peroxide (H2O2), are now known to act as cellular signalling molecules within blood vessels. In particular, these molecules can exert powerful effects on vascular tone. 2. Cerebral arteries are relatively unusual in their responsiveness to ROS. Unlike in many systemic vessels, both *O2- and H2O2 can cause vasodilatation in the cerebral microcirculation. 3. Reactive oxygen species can be produced in the vasculature via a variety of mechanisms; however, it appears that the primary source of *O2- within blood vessels is the enzyme NADPH-oxidase. 4. In cerebral vessels, activation of NADPH-oxidase causes both *O2- production and vasodilatation, indicating that NADPH-oxidase-derived ROS may have a functional role in the regulation of cerebral vascular tone. 5. Elevated levels of NADPH-oxidase activity and expression occur in cardiovascular disease states such as hypertension, atherosclerosis and subarachnoid haemorrhage. 6. Thus, ROS may contribute to the regulation of cerebral vascular tone during both physiological and pathological conditions.
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PMID:Cerebral vascular effects of reactive oxygen species: recent evidence for a role of NADPH-oxidase. 1467 50

We tested the hypothesis that the status of NO synthesis influences the renal heme-heme oxygenase system. Studies were conducted in untreated rats and rats treated with the NO synthesis inhibitor N(G)-nitro-L-arginine methyl ester for 2 days. Treated and untreated rats were contrasted in terms of renal expression of heme oxygenase-1 and -2, renal carbon monoxide (CO)-generating activity, and urinary CO concentration and excretion rate. Heme oxygenase-1 and -2 proteins were similarly expressed in the kidneys of untreated and treated rats. In contrast, the NADPH-dependent component of the CO-generating activity of renal homogenates incubated with heme (a measure of heme oxygenase activity) was higher (P<0.05) in kidneys from rats treated with the NO synthesis inhibitor relative to corresponding data in untreated rats (1015+/-95 versus 379+/-111 pmol CO/mg per hour). Similarly, relative to corresponding data in untreated rats, rats treated with the NO synthesis inhibitor displayed increased (P<0.05) urinary CO concentration (920+/-174 versus 2286+/-472 pmol/mL) and urinary CO excretion (4.7+/-0.4 versus 14.3+/-2.7 pmol/min). This study demonstrates that NO synthesis inhibition upregulates the urinary concentration and excretion rate of CO, and the HO-dependent generation of CO by renal homogenates, without affecting the expression of renal heme oxygenase isoforms. Our findings imply that endogenous NO is an inhibitory regulator of renal CO generation by HO.
Hypertension 2004 Feb
PMID:Nitric oxide synthesis inhibition promotes renal production of carbon monoxide. 1469 98

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
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PMID:The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction. 1497 55

Atherosclerosis and its complications such as coronary heart disease, myocardial infarction and stroke are the leading causes of death in the developed world. High blood pressure, diabetes, smoking and a diet high in cholesterol and lipids clearly increase the likelihood of premature atherosclerosis, albeit other factors, such as the individual genetic makeup, may play an additional role. Several epidemiological studies and intervention trials have been performed with vitamin E, and some of them showed that it prevents atherosclerosis. For a long time, vitamin E was assumed to act by decreasing the oxidation of LDL, a key step in atherosclerosis initiation. However, at the cellular level, vitamin E acts by inhibition of smooth muscle cell proliferation, platelet aggregation, monocyte adhesion, oxLDL uptake and cytokine production, all reactions implied in the progression of atherosclerosis. Recent research revealed that these effects are not the result of the antioxidant activity of vitamin E, but rather of precise molecular actions of this compound. It is assumed that specific interactions of vitamin E with enzymes and proteins are at the basis of its non-antioxidant effects. Vitamin E influences the activity of several enzymes (e.g. PKC, PP2A, COX-2, 5-lipooxygenase, nitric oxide synthase, NADPH-oxidase, superoxide dismutase, phopholipase A2) and modulates the expression of genes that are involved in atherosclerosis (e.g. scavenger receptors, integrins, selectins, cytokines, cyclins). These interactions promise to reveal the biological properties of vitamin E and allow designing better strategies for the protection against atherosclerosis progression.
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PMID:Anti-atherosclerotic effects of vitamin E--myth or reality? 1509 Feb 61

The renin-angiotensin system (RAS) is compartmented between circulating blood and tissue pericellular space. Whereas renin and its substrate diffuse easily from one compartment to another, the angiotensin peptides act in the compartment where there are generated: blood or pericellular space. Renin is trapped in tissues by low and high affinity receptors. In the target cells, angiotensin II/AT1 receptor interaction generates different signals including an immediate functional calcium-dependent response, secondary hypertrophy and a late proinflammatory and procoagulant response. These late pathological effects are mediated by NADPH oxydase-generated free oxygen radicals and NFkappaB activation. In vivo, the tissue binding of renin and the induction of converting enzyme are the main determinants of the involvement of the RAS in vascular remodeling. The target cells of interstitial angiotensin II are mainly the vascular smooth muscle cells and fibroblasts, whereas the endothelial cells and circulating leukocytes are the main targets of circulating angiotensin II. In vivo, angiotensin II participates in the vascular wall hypertrophy associated with hypertension. In diabetes, as in other localized fibrotic cardiovascular diseases, the tissue effects of angiotensin II are mainly dependent on its ability to induce TGF-beta expression. In experimental atherosclerosis, angiotensin II infusion induces aneurysm formation mediated by activation of circulating leucocytes. In these models, the administration of angiotensin II antagonists has beneficial effects on pathological remodeling. Such beneficial effects of angiotensin II antagonists in localized pathological remodeling have not yet been demonstrated in humans.
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PMID:[Renin-angiotensin system and vascular remodelling]. 1512 12

Various cardiovascular diseases including thrombosis, atherosclerosis, (pulmonary) hypertension and diabetes, are associated with disturbed coagulation. Alterations in the vessel wall common to many cardiovascular disorders have been shown to initiate the activity of the coagulation system, but also to be the result of an abnormal coagulation system. The primary link between the coagulation and the vascular system appears to be tissue factor (TF), which is induced on the surface of vascular cells and initiates the extrinsic pathway of the blood coagulation cascade, leading to the formation of thrombin. Thrombin can also interact with the vascular wall via specific receptors and can increase vascular TF expression. Such a "thrombogenic cycle" may be essentially involved in the pathogenesis of cardiovascular disorders associated with an abnormal coagulation. Therefore, the identification of the signaling pathways regulating this cycle and each of its relevant connecting links is of fundamental importance for the understanding of these disorders and their putative therapeutic potential. Reactive oxygen species (ROS) and the ROS-generating NADPH oxidases have been shown to play important roles as signaling molecules in the vasculature. In this review, we summarize the data supporting a substantial role of ROS in promoting a thrombogenic cycle in the vascular system.
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PMID:Insights into the redox control of blood coagulation: role of vascular NADPH oxidase-derived reactive oxygen species in the thrombogenic cycle. 1524 48

Diseases such as hypertension, atherosclerosis, hyperlipidemia, and diabetes are associated with vascular functional and structural changes including endothelial dysfunction, altered contractility and vascular remodeling. Cellular events underlying these processes involve changes in vascular smooth muscle cell (VSMC) growth, apoptosis/anoikis, cell migration, inflammation, and fibrosis. Many factors influence cellular changes, of which angiotensin II (Ang II) appears to be amongst the most important. The physiological and pathophysiological actions of Ang II are mediated primarily via the Ang II type 1 receptor. Growing evidence indicates that Ang II induces its pleiotropic vascular effects through NADPH-driven generation of reactive oxygen species (ROS). ROS function as important intracellular and intercellular second messengers to modulate many downstream signaling molecules, such as protein tyrosine phosphatases, protein tyrosine kinases, transcription factors, mitogen-activated protein kinases, and ion channels. Induction of these signaling cascades leads to VSMC growth and migration, regulation of endothelial function, expression of pro-inflammatory mediators, and modification of extracellular matrix. In addition, ROS increase intracellular free Ca2+ concentration ([Ca2+]i), a major determinant of vascular reactivity. ROS influence signaling molecules by altering the intracellular redox state and by oxidative modification of proteins. In physiological conditions, these events play an important role in maintaining vascular function and integrity. Under pathological conditions ROS contribute to vascular dysfunction and remodeling through oxidative damage. The present review focuses on the biology of ROS in Ang II signaling in vascular cells and discusses how oxidative stress contributes to vascular damage in cardiovascular disease.
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PMID:Reactive oxygen species and angiotensin II signaling in vascular cells -- implications in cardiovascular disease. 1527 29

Cytochrome P450 (CYP) enzymes participate in the metabolism of a variety of naturally occurring and foreign compounds by reactions requiring NADPH and O2. The diversity of reactions catalyzed and its extensive substrate specificity render CYP enzymes as one of the most versatile known catalysts. Individual members of the CYP superfamily are expressed in almost every cell type in the body. As compared to hepatic enzymes, the regulation of human extrahepatic CYPs has not been so well studied. In general, the levels of some hepatic CYP enzymes are depressed by diseases, causing potential and documented impairment of drug clearence and clinical drug toxicity. However, modulation of CYPs is enzyme selective and this selectivity differs in different diseases. This article reviews some basic concepts about CYP and its regulation in some disease states such as hypertension, diabetes, obesity and hepatic, infectious and inflammatory diseases.
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PMID:[Cytochrome P450 activity and its alteration in different diseases]. 1537 59


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