			Home About us Contact

Antagonist Losartan (antagonist + losartan)

Distribution by Scientific Domains

Medical Sciences	58%
Life Sciences	41%

Kinds of Antagonist Losartan

at1 receptor antagonist losartan

receptor antagonist losartan

Selected Abstracts

Angiotensin AT1 Receptor Antagonist Losartan and the Defence Reaction in the Anaesthetised Rat.

EXPERIMENTAL PHYSIOLOGY, Issue 3 2003
Effect on the Carotid Chemoreflex
Modulation at the level of the nucleus tractus solitarii (NTS) appears to be an effective way of controlling cardiovascular reflexes. Angiotensin II acting on angiotensin AT1 receptors at the central nervous system appears to have an important role in these modulatory processes. The hypothalamic defence area (HDA) is a potential source of descending fibres containing angiotensin II that innervate the NTS. We investigated the effect of AT1 receptor blockade in the NTS on the response to stimulation of HDA in anaesthetised rats treated with the neuromuscular blocking agent pancuronium bromide. The characteristic increase in heart rate, blood pressure and phrenic nerve activity evoked by electrical stimulation of HDA is decreased by the microinjection of the AT1 receptor antagonist losartan into the NTS and the cardiovascular response to carotid body chemical stimulation is also reduced. These results support the hypothesis that AT1 receptors in the NTS play a role in the modulation of cardiovascular reflexes, and modify the influence exerted on the processing of these reflexes by other areas of the central nervous system. [source]

Type 2 Diabetes: RENAAL and IDNT,The Emergence of New Treatment Options

JOURNAL OF CLINICAL HYPERTENSION, Issue 1 2002
Domenic A. Sica MD
The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies,the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL),were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme,that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy. [source]

Losartan modifies glomerular hyperfiltration and insulin sensitivity in type 1 diabetes

DIABETES OBESITY & METABOLISM, Issue 6 2001
S. Nielsen
Aim: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. Methods: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 ± 7 years (mean ±,s.d.), HbA1c 8.1 ± 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. Results: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 ± 11/8 vs. 130/76 ± 12/6 mmHg, p <,0.05). A significant decline in GFR (133 ± 23 vs. 140 ± 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 ± 3.5 vs. 26.2 ± 3.6%, p <,0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 ± 0.53 vs. 2.98 ± 0.93 mg/kg/min) and insulin-stimulated states (6.84 ± 2.52 vs. 6.97 ± 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 ± 0.34 vs. 1.33 ± 0.18, mg/kg/min, p <,0.01) and during insulin stimulation (2.89 ± 0.75 vs. 2.40 ± 0.62 mg/kg/min, p <,0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. Conclusions: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients. [source]

Angiotensin-(1,7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity

EXPERIMENTAL PHYSIOLOGY, Issue 5 2008
Jorge F. Giani
Angiotensin (ANG) II contributes to cardiac remodelling by inducing the activation of several signalling molecules, including ERK1/2, Rho kinase and members of the STAT family of proteins. Angiotensin-(1,7) is produced in the heart and inhibits the proliferative actions of ANG II, although the mechanisms of this inhibition are poorly understood. Accordingly, in the present study we examined whether ANG-(1,7) affects the ANG II-mediated activation of ERK1/2 and Rho kinase, STAT3 and STAT5a/b in rat heart in vivo. We hypothesized that ANG-(1,7) inhibits these growth-promoting pathways, counterbalancing the trophic action of ANG II. Solutions of normal saline (0.9% NaCl) containing ANG II (8 pmol kg,1) plus ANG-(1,7) in increasing doses (from 0.08 to 800 pmol kg,1) were administered via the inferior vena cava to anaesthetized male Sprague,Dawley rats. After 5 min, hearts were removed and ERK1/2, Rho kinase, STAT3 and STAT5a/b phosphorylation was determined by Western blotting using phosphospecific antibodies. Angiotensin II stimulated ERK1/2 and Rho kinase phosphorylation (2.3 ± 0.2- and 2.1 ± 0.2-fold increase over basal values, respectively), while ANG-(1,7) was without effect. The ANG II-mediated phosphorylation of ERK1/2 and Rho kinase was prevented in a dose-dependent manner by ANG-(1,7) and disappeared in the presence of the Mas receptor antagonist d -Ala7 -ANG-(1,7). Both ANG II and ANG-(1,7) increased STAT3 and STAT5a/b phosphorylation to a similar extent (130,140% increase). The ANG-(1,7)-stimulated STAT phosphorylation was blocked by the AT1 receptor antagonist losartan and not by d -Ala7 -ANG-(1,7). Our results show a dual action of ANG-(1,7), that is, a stimulatory effect on STAT3 and 5a/b phosphorylation through AT1 receptors and a blocking action on ANG II-stimulated ERK1/2 and Rho kinase phosphorylation through Mas receptor activation. The latter effect could be representative of a mechanism for a protective role of ANG-(1,7) in the heart by counteracting the effects of locally generated ANG II. [source]

Angiotensin AT1 Receptor Antagonist Losartan and the Defence Reaction in the Anaesthetised Rat.

Effect of Losartan on Sodium Appetite of Hypothyroid Rats Subjected to Water and Sodium Depletion and Water, Sodium and Food Deprivation

EXPERIMENTAL PHYSIOLOGY, Issue 5 2001
D. Badauê-Passos Jr
The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg g,1, the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg g,1 did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors. [source]

Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010
María I. Rosón
The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague,Dawley rats were infused for 2,h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10,mg,kg,1 in bolus) (Na,Los group), or plus the superoxide dismutase mimetic tempol (0.5,mg,min,1,kg,1) (Na,Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FENa) were measured. Ang II, NF-,B, hypoxia inducible factor-1, (HIF-1,), transforming growth factor ,1 (TGF-,1), smooth muscle actin (,-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-,B, and TGF-,1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1, immunostaining, lower eNOS expression, and unmodified ,-SMA. Losartan and tempol increased FENa in sodium overload group. Although losartan reduced Ang II and NF-,B staining and increased eNOS expression, it did not restore HIF-1, expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1, expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1, and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1, expression and down-regulating TGF-,1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. J. Cell. Physiol. 224:41,48, 2010 © 2010 Wiley-Liss, Inc. [source]

The Receptors and Role of Angiotensin II in Knee Joint Blood Flow Regulation and Role of Nitric Oxide in Modulation of Their Function

MICROCIRCULATION, Issue 5 2003
H. NAJAFIPOUR
ABSTRACT Objectives: Angiotensin-converting enzyme (ACE) upregulation in the stroma cells of arthritis rheumatoid joints may produce a higher tissue concentration of angiotensin II (angII), which is a vasoconstrictor and mitogen factor that causes local hypoxia and synovial proliferation. No study in the literature has examined the role of angII in joint blood flow (JBF) regulation and the potential effect of ACE inhibitors on JBF. Methods: The study was performed on 20 Dutch white rabbits to examine the JBF response to angII, angII receptor subtypes, and the role of nitric oxide (NO) in angII effects in knee joint blood vessels. Drugs were administered locally through retrograde saphenous artery cannulation. Joint vascular resistance (JVR) was calculated by dividing the arterial blood pressure by the JBF. Results: AngII increased JVR dose dependently. The angII type 1 (AT1) receptor antagonist losartan did not change the basal JVR but completely blocked the effect of angII on JVR. N, -nitro-L-arginin methyl ester (L-NAME) increased JVR by a mean (±SEM) of 25.8 ± 8.7% (p < 0.05) but did not affect the joint vessel response to angII and losartan. Conclusions: AngII receptors are from the AT1 subtype in normal joint blood vessels, but angII plays no significant role in JBF regulation. The basal release of NO plays a role in resting JBF regulation, but NO does not affect the AT1 receptor-mediated vasoconstriction of joint blood vessels. [source]

Losartan reduces the costs of diabetic end-stage renal disease: An Asian perspective

NEPHROLOGY, Issue 5 2005
WONG KOK SENG
SUMMARY: Objective: To evaluate losartan and conventional antihypertensive therapy (CT) compared with CT alone on the cost associated with end-stage renal disease (ESRD) in Hong Kong, Japan, Korea, Malaysia, Singapore and Taiwan. Methods: Reduction of end-points in non-insulin-dependent diabetes mellitus with the angiotensin II antagonist losartan (RENAAL) was a multinational, double-blind, randomized, placebo-controlled trial to evaluate the renal protective effects of losartan on a background of CT in patients with type 2 diabetes and nephropathy. The primary composite end-point was a doubling of serum creatinine, ESRD or death. Data on the duration of ESRD for the Asian subgroup of patients enrolled in RENAAL were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the number of days each patient experienced ESRD with the average daily cost of dialysis from the third-party payer perspective in Hong Kong, Japan, Korea, Malaysia, Singapore and Taiwan. Total cost, converted to US dollars, was the sum of ESRD and losartan costs. Results: Losartan plus CT reduced the number of days with ESRD by 37.9 per patient over 3.5 years compared with CT alone. This reduction in ESRD days resulted in a decrease in the cost associated with ESRD, which ranges from $910 to $4346 per patient over 3.5 years across the six countries or regions. After accounting for the cost of losartan, the reduction in ESRD days resulted in net savings in each of the six countries or regions, ranging from $55 to $515 per patient. Conclusion: Treatment with losartan in patients with type 2 diabetic nephropathy not only reduced the incidence of ESRD among Asian patients, but resulted in direct medical cost savings in countries or regions representing Asia. [source]

Angiotensin I-converting enzyme is expressed by erythropoietic cells of normal and myeloproliferative bone marrow

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2003
Maruska Marusic-Vrsalovic
Summary. It is proposed that a locally active, intrinsic renin,angiotensin system (RAS) exists in the bone marrow (BM) and plays a role in regulating haematopoiesis. Angiotensin II type I receptor has been detected on erythroid burst-forming unit-derived cells; its antagonist losartan and angiotensin I-converting enzyme (ACE) inhibitors can suppress erythropoiesis. The possible role of ACE/RAS in BM was investigated by evaluating ACE expression in normal BM, several myeloproliferative disorders and myelodysplasia. Immunohistochemical studies showed that erythroid elements expressed ACE protein in both normal and disturbed haematopoiesis. The presence of ACE in erythroid cells suggests another mechanism for direct ACE inhibitor activity in erythropoiesis. [source]

Effects of the angiotensin II receptor blocker losartan on the monocyte expression of biglycan in hypertensive patients

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2010
Maria A Sardo
Summary 1.,Recently, we demonstrated that biglycan (BGN) is increased in circulating monocyte cells from hypertensive patients and that angiotensin (Ang) II is able to increase BGN expression. The present study was designed to investigate the effects of treatment with the angiotensin AT1 receptor antagonist losartan on monocyte BGN mRNA and protein expression in essential hypertension. 2.,One hundred and twenty-six newly diagnosed hypertensive patients without additional risk factors for atherosclerosis and cardiovascular disease were treated with 100 mg losartan once daily for 6 months. Biglycan mRNA and protein expression was determined in monocytes isolated from peripheral blood before (T0) and after (T1) therapy. Plasma levels of interleukin (IL)-6, tumour necrosis factor (TNF)-, and high sensitivity C-reactive protein (hs-CRP) were also determined. In addition, BGN mRNA and protein expression was determined after the ex vivo addition of 1 ,mol/L AngII to monocytes isolated from 20 randomly selected hypertensive patients. 3.,Biglycan mRNA and protein expression, blood pressure and plasma levels of fibrinogen, IL-6, TNF-, and CRP were significantly lower at T1 than at T0. Variations in BGN expression were associated with inflammatory markers, but not directly with blood pressure. In AngII-stimulated monocytes, BGN mRNA and protein expression was significantly lower at T1 that at T0. Moreover, mean BGN mRNA expression in AngII-stimulated monocytes isolated from losartan-treated patients was similar to baseline expression in unstimulated monocytes from untreated patients. 4.,The results of the present study show that losartan can reduce BGN expression in monocytes from hypertensive patients, without any linear association with blood pressure, suggesting that the effects of AngII on BGN expression in monocytes may be modulated, in part, by an AT1 receptor blocker. [source]

Altered Mitogen-Activated Protein Kinase Activation In Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2002
Takao Kubo
SUMMARY 1.,We previously reported that activation function of mitogen-activated protein kinases (MAPK) is enhanced in aorta strips from both prehypertensive and hypertensive spontaneously hypertensive rats (SHR) and that this enhancement of MAPK activation results from enhanced MAPK activation reactivity to angiotensin (Ang) II in SHR aorta strips. 2.,The purpose of the present study was to examine whether the enhanced function of the vascular angiotensin system observed in SHR aorta strips results from genetic alterations of vascular smooth muscle cells from SHR. 3.,Basal MAPK activity was within normal limits in cells from 4-week-old SHR, whereas enzyme activity was enhanced in 9-week-old SHR compared with age-matched Wistar-Kyoto (WKY) rats. 4.,Mitogen-activated protein kinase activation reactivity to AngII and endothelin-1 was enhanced in 9-week-old SHR cells but not in 4-week-old SHR cells. The enhancement of basal MAPK activity in 9-week-old SHR cells was abolished by a combination of the angiotensin AT1 receptor antagonist losartan and the endothelin receptor antagonist BQ123. 5.,These findings suggest that MAPK activation function in 4-week-old SHR cells is not enhanced. Thus, it appears that factors outside vascular smooth muscle cells are needed for the enhanced MAPK activation observed in 4-week-old SHR aorta strips. In 9-week-old SHR, MAPK activation function is enhanced in cells themselves and this function may, at least in part, contribute to the enhanced MAPK activation observed in SHR aorta strips. [source]