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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies, we have shown that losartan possesses nitric oxide-dependent antithrombotic properties in various models of hypertension in rats. It was demonstrated that stimulation of AT2-receptors plays an important role in the pharmacological effects of AT1-receptor antagonists. Thus, in this study, we examine the participation of AT2-receptors in the antithrombotic action of losartan in renal hypertensive rats on venous thrombosis induced by a two-hour ligation of the vena cava. Losartan administration(30 mg/kg, p.o.) resulted in a marked decrease in thrombus weight (by 85%, p<0.001). PD123319, an AT2-receptor antagonist (10 mg/kg, i.v.), administered concomitantly with losartan, abolished its antithrombotic effect, whilst it had no influence on thrombus weight when given alone. A significant decrease in systolic blood pressure was observed in animals given losartan. PD123319 administration didnot abolish this action of losartan and did not alter blood pressure when given alone. No changes in prothrombin time, activated partial thromboplastin time, or euglobulin clot lysis time were observed in animals administered losartan and/or PD123319.Similarly, primary haemostatics evaluated by bleeding time and platelet count did not change in any group of rats. In conclusion, we have shown that AT2-receptor stimulation is involved in the antithrombotic action of losartan in renal hypertensive rats.
J Renin Angiotensin Aldosterone Syst 2000 Sep
PMID:The involvement of AT(2)-receptor in the antithrombotic effect of losartan in renal hypertensive rats. 1188 Oct 35

The effects of the specific angiotensin II (Ang II) AT1-receptor blocker valsartan on events related to restenosis were investigated in rabbits after common carotid balloon injury. Six animals were given valsartan from two days prior to injury until 14 days post-injury. Three control groups (n=6 in each group) were either sham-operated, untreated or treated with the angiotensin-converting enzyme (ACE) inhibitor,captopril. Both ACE inhibition and AT,-receptor blockade had marked effects on plasma levels of endothelin ET1, thromboxane TXB2 and 6-keto-PGF1-alpha. The most dramatic effects on ET, levels were seen in rabbits treated with valsartan, where levels were reduced to values close to those for sham-operated animals (96.85 vs. 86.45 pg/ml). Captopril treatment led to a statistically significant (p<0.01) reduction in ET1 levels compared with untreated animals, but the reduction was only about half that seen with AT1-receptor blockade. TXB2 levels doubled (202.58 vs.413.28 pg/ml) upon arterial injury in control animals but rose by only 20-35% in rabbits treated with captopril (246.45 pg/ml) or valsartan (268.13). In untreated animals, 6-keto-PGF1-alpha levels decreased slightly after injury, but for both the captopril and valsartan groups, there were significant increases in levels of this prostaglandin derivative, effects attributed to the action of bradykinins. Levels were highest in the captopril-treated animals. Valsartan and captopril treatment led to a significant reduction in neointimal thickness and the extent of lumen stenosis compared with untreated animals. Both treatments were effective in reducing neointimal area and significantly (p<0.05)reduced cell proliferation. The differences between treatments can be attributed to the different actions of the agents, as valsartan leaves the AT2-receptor unblocked, while captopril, through inhibition of Ang II synthesis, prevents stimulation of both receptors.A combination of both treatments may be a possible way forward in the clinical prevention of restenosis.
J Renin Angiotensin Aldosterone Syst 2001 Mar
PMID:Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade. 1188 Oct 60

Previous studies have shown that angiotensin II (Ang II), by mediating rapid recruitment of collateral circulation, has a protective effect in the setting of acute ischaemia. In an experimental model of acute cerebral ischaemia in the gerbil, Fernandez et al. have reported that the mechanism of the protective effect of Ang 11 is blood pressure (BP)-independent, and that the AT1-receptor antagonist, losartan, but not the ACE inhibitor (ACE-I),enalapril, decreases mortality following unilateral carotid artery ligation. The aim of this study was to examine there producibility of the respective effects of losartan and enalapril, and to verify that these differential effects are drug class-related. Acute cerebral ischaemia was induced in anaesthetised gerbils bv unilateral carotid ligation. The effect of pretreatment with two different ACE-I(enalapril and lisinopril), and two different AT1-receptor antagonists (losartan and candesartan), administered orally or intravenously, on mortality were compared. Kaplan-Meier survival curves at day three were analysed bv a log-rank test. Pretreatment with both enalapril and lisinopril significantly decreased survival at day three compared with controls, while the AT1-receptor antagonists losartan and candesartan, despite similarly lowering BP, did not increase mortality. Coadministration of losartan and enalapril increased mortality to the same extent as enalapril alone. This study confirms that Ang II contributes to protective mechanisms against acute cerebral ischaemia through non AT1-receptor-mediated, BP-independent effects.
J Renin Angiotensin Aldosterone Syst 2001 Jun
PMID:Non-AT(1)-receptor-mediated protective effect of angiotensin against acute ischaemic stroke in the gerbil. 1188 Nov 7

Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9+/-7.6 years, range 23-49 years, BMI; 27.6+/-3.7kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.
J Renin Angiotensin Aldosterone Syst 2001 Jun
PMID:Effects of losartan treatment on T-cell activities and plasma leptin concentrations in primary hypertension. 1188 Nov 9

We assessed the effects of the angiotensin II (Ang II) type 1 receptor (AT1-receptor) blocker, candesartan, (CN, 1 mg/kg i.v. over 30 minutes pre-ischaemia) alone or after intracoronary administration of Ang II type 2 receptor (AT2-receptor) blocker (PD 123319), protein kinase C (PKC) inhibitor (chelerythrine), endothelial nitric oxide (NO) synthase inhibitor (N(G)-monomethyl-L-arginine or L-NMMA), and bradykinin (BK) -B2 receptor inhibitor (HOE140) on in vivo left ventricular (LV) function and remodelling (echocardiograms/Doppler) and haemodynamics in 30 dogs with reperfused anterior infarction (90 minutes ischaemia, 120 minutes reperfusion), and ex vivo infarct size, AT1-receptor/AT2-receptor proteins and PKC(epsilon) (immunoblots), and cyclic guanosine 3', 5' monophosphate (cGMP, immunoassay). Compared with controls, CN inhibited the Ang II pressor response, reduced LV preload, improved LV systolic and diastolic function, limited LV remodelling, decreased infarct size, and increased AT2-receptor and PKC(epsilon) proteins in the infarct zone (IZ), and these responses were abrogated by PD 123319, chelerythrine, L-NMMA and HOE140. In addition, the increase in LV cGMP with CN was attenuated by PD 123319, L-NMMA and HOE140. The overall results suggest that AT2-receptor activation and signalling via BK, PKC(epsilon) and cGMP contribute to cardioprotection associated with AT1-receptor blockade during ischaemia-reperfusion injury.
J Renin Angiotensin Aldosterone Syst 2001 Jun
PMID:Enhanced regional AT(2)-receptor and PKC(epsilon) expression during cardioprotection induced by AT(1)-receptor blockade after reperfused myocardial infarction. 1188 Nov 13

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 (MMP-1) in endothelial cell cultures from human coronary arteries. These increases were completely prevented by the addition of 10 microM valsartan or candesartan and partially by the addition of lower concentrations of these drugs, i.e. 1 microM and 0.1 microM. No significant difference between the effect of the two AT1-receptor antagonists was observed. These results suggest that AT1-receptor antagonists not only can reduce blood pressure by blocking the action of Ang II, but might also contribute to the prevention of atherogenesis and plaque instability.
J Renin Angiotensin Aldosterone Syst 2001 Jun
PMID:Valsartan and candesartan can inhibit deteriorating effects of angiotensin II on coronary endothelial function. 1188 Nov 14

Angiotensin II (Ang II) regulates cerebral blood flow by stimulating cerebral vasoconstriction via AT1-receptors. In adult spontaneously hypertensive rats (SHR), the cerebrovascular autoregulatory curve is shifted to the right, in the direction of higher blood pressures, an indication of excessive cerebrovascular vasoconstriction. A restricted capacity to dilate cerebral blood vessels may be responsible for the enhanced vulnerability to cerebrovascular ischaemia during hypertension. We found that chronic treatment with the AT1-receptor antagonist, candesartan, (0.5 mg/kg/day for 14 days, via osmotic minipumps implanted in the subcutaneous tissue) blocked Ang II binding to AT1-receptors in cerebral blood vessels and in brain areas involved in the regulation of cerebrovascular flow, and increased the ratio of lumen-wall area in the middle cerebral artery. Candesartan treatment normalised the lower part of the autoregulatory curve in SHR, and markedly decreased cerebral ischaemia as a consequence of middle cerebral artery occlusion with reperfusion. Protection from ischaemia is related to arterial remodelling, enhanced compensatory vasodilatation in the peripheral area of ischaemia, decreased reduction in cerebral blood flow following the occlusion of a major cerebral blood vessel, and protection from injury in the periphery of the lesion. Our results indicate that pre-treatment with AT1-antagonists such as candesartan could be of benefit in the prevention and treatment of brain ischaemia.
J Renin Angiotensin Aldosterone Syst 2001 Sep
PMID:Pre-treatment with candesartan protects from cerebral ischaemia. 1188 Nov 19

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT2-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control group. CBF was measured by the intracarotid 133xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline CBF, but resulted in a minor BP decrease (10 control and 10 treated rats). The lower limit of CBF autoregulation (eight treated and eight control) as well as the upper limit of CBF autoregulation (eight treated and eight control) were not significantly different in PD 123319 and control animals (lower limit treated 102+/-4 mmHg and control 94+/-4; NS, and upper limit treated 171 +/- 10 mmHg and control 162+/-7; NS). These findings indicate that acute AT2-receptor blockade does not influence CBF autoregularion.
J Renin Angiotensin Aldosterone Syst 2001 Sep
PMID:No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation. 1188 Nov 21

The effect on renal function and efficacy of the angiotensin II AT1-receptor blocker (ARB), telmisartan, were compared with those of the angiotensin-converting enzyme inhibitor, enalapril, for the treatment of mild-to-moderate hypertension (diastolic blood pressure [DBP] 95-114 mmHg) in the presence of moderate renal failure (creatinine clearance [Ccr] 30-80 ml/minute). The study was multicentre, double-blind, double-dummy and active-controlled in design, with patients randomised in a 2:1 ratio to receive telmisartanor enalapril. After a two-week placebo run-in period, the 71 eligible patients received either telmisartan, 40 mg, orenalapril, 10 mg, once-daily for four weeks. Thereafter, doses were titrated to telmisartan 80 mg or enalapril 20 mg once-daily if supine trough DBP was still > or =90 mmHg. After a further four weeks, dose titration was again performed, as required, to telmisartan, 80 mg,or enalapril, 20 mg, or frusemide was given in addition if the double dose was already being administered. Mean Ccr decreases of 4.6% for telmisartan and 2.8% forenalapril were not clinically significant. Adverse events occurred in 12 (26.7%) telmisartan-treated patients and in 12 (46.2%) patients receiving enalapril. The mean reduction in supine trough DBP from baseline to the last available value was 12.5 mmHg for telmisartan,compared with 11.9 mmHg for enalapril. A full (reduction of >or=10 mmHg) or partial (reduction of 7-9 mmHg) response occurred in 78% of telmisartanpatients and 65% of enalapril patients. In the enalapril group, 43% of patients required frusemide, compared with 29% of those in the telmisartan group. In conclusion, telmisartan lacks detrimental effect on renal function, is effective in the treatment of mild-to-moderate hypertension in patients with moderate renal failure,and is comparable to enalapril.
J Renin Angiotensin Aldosterone Syst 2001 Dec
PMID:Evaluation of the safety and efficacy of telmisartan and enalapril, with the potential addition of frusemide, in moderate-renal failure patients with mild-to-moderate hypertension. 1188 Nov 31

Studies performed in the last five years have led to the knowledge of new mechanisms by which the hypertensive process produces hypertrophy and cardiac fibrosis, at the same time, favoring development of the atheroesclerotic plaque. The Renin-Angiotensin-Aldosterone axis is relevant by involved in the physiopathology of these alterations, not only by producing hyperplasia and hypertrophy of vascular smooth muscle cells or by increasing protein and DNA syntheses, mediated by Angiotensin II (by itself a potent Growth factor) but also through inflammatory processes exerted upon the vascular smooth muscle cells. These alterations (hypertrophy, fibrosis, inflammation, and destabilization of the atherosclerotic plaque) can now be counteracted by blocking the Angiotensin-Converting enzyme or its AT1 receptors with the consequent improvement in ventricular diastolic functions.
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PMID:[The heart in hypertension. Cardiac protection and cardiac repair]. 1200 49


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