We studied the gradual onset of pressure overload (PO) induced by a mildly constricting aortic band in 8-wk-old puppies (n = 8) that increased to 98 +/- 11 mmHg at 9 mo. Left ventricular (LV) weight/body weight was increased in PO versus sham-operated littermate controls [8.11 +/- 0.60 (SE) vs. ...

Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EETs to dihydroxyeicosatrienoic acids (DHETs) that are void of effects on the ...

BACKGROUND: Angiotensin II induces both cardiac and vascular smooth muscle (VSM) hypertrophy. Recent studies suggest a central role for a phagocyte-type NADPH oxidase in angiotensin II-induced VSM hypertrophy. The possible involvement of an NADPH oxidase in the development of cardiac hypertrophy has not been studied. Methods and Results- Mice with ...

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), ...

Clinical data and experimental studies have established the important role of abnormal lipid metabolism in the causation of atherosclerosis and enthroned the hydroxymethylglutaryl coenzyme reductase inhibitors (statins) as a mainstay in management of patients with coronary heart disease. However, emerging experimental data underline the role of vascular renin-angiotensin systems in ...

Newer classes of antihypertensive agents, such as angiotensin II receptor antagonists, may offer benefits to patients in addition to their ability to lower blood pressure. It is accepted that chronic hypertension contributes to the development of cerebrovascular and cardiovascular disease, and several studies have demonstrated a link between hypertension and ...

We determined the short-term intra-individual variability for each parameter of the Heidelberg Retina Tomograph II (HRT II). Therefore we examined prospectively 20 healthy volunteers 3 times within 2 weeks. The variability was expressed as the coefficient of variation for each parameter. The short-term intra-individual variability in normal subjects was < ...

BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous ...

Long considered independent risk factors for end-stage vascular disease, hypertension and atherosclerosis may be intimately linked through their effects on vascular endothelial dysfunction, which are mediated by the renin-angiotensin system (RAS). Angiotensin II, a potent vasoconstrictor and the principal active peptide of the RAS, can also produce structural changes in ...

3-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5-(methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a quinazoline derivative, exhibits alpha 1 -adrenoceptor antagonistic and type I antiarrhythmic effects on mammalian cardiac tissues. In the current study, the effects of DL-017 on the hemodynamic profile in anesthetized, spontaneously hypertensive rats were evaluated. Intravenous administration of DL-017 induced dose-dependent reductions of heart rate and blood ...

1. The participation of endothelin (ET) in the development and maintenance of hypertension induced by angiotensin (Ang) II was assessed using the non-specific ET receptor antagonist bosentan (30 mg/kg per day). 2. In the prevention study, bosentan was given 24 h prior to and during the 17 day period of ...

The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in ...

Non-modulation has been suggested as a possible intermediate phenotype defining a subgroup of genetic hypertension. The trait is characterized by an attenuated response of renal blood flow and/or aldosterone to angiotensin (Ang) II. We tested the hypothesis that functional polymorphisms of the core promoter of the angiotensinogen gene are associated ...

1. Melanotan-II had been reported to cause penile erections in men with erectile dysfunction. In the present study, we investigated the mechanisms by which systemic administration of MT-II increases intracavernosal pressure in anaesthetized rabbits. 2. MT-II (10 microM) had no effect on electrical field stimulation-evoked relaxations of rabbit corpus cavernosal ...

The aim of this work was to evaluate the potential of liposomes as a tool for the sustained release of the short half-life peptides of the renin-angiotensin system in a specific site of the brain. Angiotensin (Ang)-(1-7) was selected for this study because of its known cardiovascular effects at the ...

Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries. Multiple growth factors and ...

It is widely accepted that in women, estrogens provide protection against the development of cardiovascular disease. However, the cardiovascular role of estrogens in men remains uncertain, despite preliminary evidence that endogenous estrogens produced by aromatization of androgenic precursors are of physiological importance. Hypogonadal men have very low levels of circulating ...

Recent advances in the understanding of vascular disease genesis suggest that atherosclerosis and hypertension, primary targets of therapy in the INternational VErapamil SR/trandolapril STudy (INVEST), are closely related. A unified model for the development of cardiovascular disease (CVD) is emerging from recent advances related to atherosclerosis and hypertension. The process ...

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFalpha levels in heart failure has not yet been studied. We evaluated the effect of losartan ...

OBJECTIVES: We investigated the changes in coronary vascular resistance caused by angiotensin II, angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 or 2 receptor (AT(1)R and AT(2)R, respectively) antagonists in chronic heart failure (CHF). BACKGROUND: Angiotensin II is an intense vasoconstrictor, and increased angiotensin II in CHF might exert ...

Left ventricular hypertrophy (LVH) is a cardiovascular risk factor. A possible role for endothelial dysfunction in this condition was investigated in a Dunkin-Hartley guinea pig aortic-banded pressure overload-induced model of LVH. Aortic banding produced significant elevation of fore- and hindlimb blood pressure (BP), heart-to-body weight ratios, plasma angiotensin II (ANG ...

The mechanisms mediating the activation of cardiac gene expression during pressure overload are not fully understood. We examined whether angiotensin II-induced activation of ventricular gene expression is related to blood pressure and ventricular mass or requires other factors by infusing angiotensin II in sham-operated and adrenalectomized rats. In sham-operated rats, ...

OBJECTIVES: To examine the dose response relationship between Ang II and pulse wave velocity (an index of arterial stiffness) in healthy human volunteers. DESIGN AND METHODS: We studied 9 healthy male volunteers (mean age 24.7 +/- 0.66 years) in a double-blind, randomized, cross-over, placebo-controlled design. We measured carotid-femoral PWV using ...

BACKGROUND: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are ...

Participation of central cholinergic system in the effects of intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) on blood pressure and heart rate was studied in conscious, freely moving rats. Ang II dose-dependently increased blood pressure and decreased heart rate. Both atropine and mecamylamine (i.c.v.) pretreatments prevented the cardiovascular effects ...

In a patient who was taking an angiotensin-converting-enzyme inhibitor, low-density lipoprotein (LDL) apheresis with dextran-sulfate cellulose provoked hypotension accompanied by lacrimation and blurred vision. Hypotension was eliminated by changing the anticoagulant from heparin to a protease inhibitor, nafamostat mesilate. A study was undertaken to clarify whether an antagonist of angiotensin ...

Angiotensin II (Ang II), the effector peptide of the renin-angiotensin system (RAS), exerts a variety of actions in physiological blood pressure and body fluid regulation, and is implicated as a major pathogenic factor in the development of cardiovascular disease. Inhibition of the RAS, via treatment with the angiotensin-converting enzyme inhibitors ...

Recent studies indicate that baroreflex suppression of renal sympathetic nerve activity is sustained for up to 5 days of ANG II infusion; however, steady-state conditions are not associated with ANG II hypertension of this short duration. Thus the major goal of this study was to determine whether neurally induced increments ...

BACKGROUND: The role of load versus angiotensin II (Ang II) and endothelin-1 (ET) in the pathogenesis of hypertensive heart disease is controversial. We sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results-- Bilateral renal ...

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to lower hematocrit and erythropoietin (EPO), but a direct link between angiotensin II (Ang II) and EPO in humans has not been shown. METHODS: Placebo or Ang II was infused for six hours in nine healthy male volunteers with and without blockade ...

Inflatable insert products used to overcome residual limb shrinkage were evaluated in a bench test environment under compressive loading conditions. Pressure-loss tests under static loading demonstrated that after inserts were inflated to 43.4 to 45.6 kPa, insert pressures reduced from 0.09%/min to 1.36%/min in the first 5 min and from ...

We cloned a rat vascular chymase (RVCH) from smooth muscle cells (SMCs) that converts angiotensin I to II and is up-regulated in SMC from spontaneously hypertensive vs. normotensive rats. To determine whether increased activity of RVCH is sufficient to cause hypertension, transgenic mice were generated with targeted conditional expression of ...

Children with end-stage renal disease (ESRD) often remain hypertensive despite bilateral nephrectomy and aggressive fluid removal on hemodialysis. We speculated that an extrarenal source of renin might contribute to the release of "tissular" angiotensin-II (AT-II) generating hypertension in anephric patients. At the same time, experimental evidence supports that peripheral AT-II ...

The aim of this investigation was to compare the contribution of brain angiotensin II in mediating the transmission of a somatosensory stimulus within the brain to generate a renal sympathetic nerve-dependent antidiuresis and antinatriuresis in normotensive Wistar rats and stroke-prone spontaneously hypertensive rats (SHRSP). In anesthetized Wistar rats, stimulation of ...

Urotensin II (U-II) is a cyclic peptide, recently cloned in man and present in cardiac tissue and arteries. The effects of human U-II (hU-II) on coronary perfusion pressure (CPP) were investigated in isolated rat hearts perfused retrogradely via the aorta at constant flow. hU-II produced a concentration-dependent increase in CPP ...

BACKGROUND: Renal kallikrein has been linked with inheritance of arterial hypertension and with sensitivity to drug nephrotoxicity. Identification of a cause--effect relationship between low kallikrein and intermediate phenotypes has been hampered by the lack of adequate animal models. METHODS: Kallikrein was measured in tissues obtained from rats inbred for low ...

The angiotensin II (Ang II) AT1-receptor antagonists, valsartan and candesartan, were compared with regard to their effect on Ang II-mediated changes in parameters of coronary endothelial function. Ang II (10 microM) induced increased concentrations of the vasoconstrictor endothelin, the procoagulatory substance plasminogen-activator-inhibitor-1 (PAI-1) and the precursor of the matrix-metalloproteinase 1 ...

The effect of an intravenous bolus injection of the type 1 angiotensin II receptor antagonist, losartan on haemodynamics after right heart infarct was studied in an experimental setting. Right heart infarct was induced in twelve young swine and losartan was given in a bolus intravenous dose one hr later to ...

BACKGROUND: Prolonged angiotensin-converting enzyme (ACE) inhibitor therapy leads to angiotensin I (Ang I) accumulation, which may "escape" ACE inhibition, generate Ang II, stimulate the Ang II subtype 1 (AT1) receptor, and exert deleterious renal effects in patients with chronic renal diseases. We tested the hypothesis that losartan therapy added to ...

Blood pressure (BP) response to infused angiotensin II (Ang II) has been widely used to characterize hypertensive subjects. High cholesterol levels have recently been found to enhance this response in young men, suggesting an important new link between atherosclerosis and hypertension. The present study assessed the familial resemblance of the ...

Among the main bioactive peptides of the brain renin-angiotensin system, angiotensin (Ang) II and AngIII exhibit the same affinity for type 1 and type 2 AngII receptors. Both peptides, injected intracerebroventricularly, cause similar increases in vasopressin release and blood pressure. Because AngII is converted in vivo to AngIII, the identity ...

We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks ...

To examine the actions of angiotensin II on regional vascular resistances, we monitored regional blood flows and cardiac output with transit-time flow probes and thermodilution, respectively, in anesthetized rats. To remove the influence of endogenous angiotensin II, rats were pretreated with captopril (30 mg/kg intravenously). Intravenous infusions of angiotensin II ...

The role of the renin-angiotensin system in the regulation of normal blood pressure and in the pathogenesis of hypertension has long been appreciated. Angiotensin II (Ang II) was originally thought to only influence blood pressure, but the results of many preclinical and clinical studies now suggest that Ang II has ...

Hypertension is associated with a number of adverse morphologic and functional changes in the cardiovascular system. These include remodeling of the left ventricle, alterations in the morphology and mechanical properties of the vasculature, and the development of endothelial dysfunction. Recent studies have shown that angiotensin II is capable of mediating ...

Renin was first isolated in the kidney by Tigerstedt and Bergman over 100 years ago. Almost 50 additional years were necessary to isolate the renin substrate angiotensinogen and to show its cleavage to angiotensin (Ang). Further studies were then needed to demonstrate that Ang I is converted via an angiotensin-converting ...

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) ...

The proximal tubule synthesizes and luminally secretes high levels of angiotensin II, which modulate proximal tubule transport independently of systemic angiotensin II. The purpose of this in vivo microperfusion study is to examine whether the renal nerves modulate the effect of intraluminal angiotensin II on proximal tubule transport. The decrement ...

OBJECTIVE: The goals of this study were to characterize the effects of angiotensin II (Ang II) on renal sympathetic nerve activity (RSNA) and to define mechanisms of its actions in mice. DESIGN: The experiments were performed in sodium pentobarbital anesthetized C57BL/6J mice to investigate the effects of intravenous administration of ...

We previously reported the generation of transgenic mice containing the entire human renin gene with a 900-bp promoter. To determine whether all the required elements for angiotensin II-mediated suppression of human renin are present in these mice, angiotensin II was chronically infused by means of osmotic minipump at both low ...