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AT1 Receptor Antagonist Losartan (at1 + receptor_antagonist_losartan)

Distribution by Scientific Domains

Life Sciences	66%

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]

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.

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]

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]