Disease relevance of losartan

• The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo) [1].
• Losartan-induced azotemia in a diabetic recipient of a kidney transplant [2].
• CONCLUSION: These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH [3].
• Losartan and severe migraine [4].
• Angiotensin-converting enzyme inhibitors and losartan, an angiotensin II type 1 receptor (AT1) antagonist, ameliorate posttransplant erythrocytosis, without altering serum erythropoietin levels [5].

Psychiatry related information on losartan

• RESULTS: A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02) [1].
• CONCLUSIONS : Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments [6].
• 3. When given after 6 h of water deprivation, losartan and EXP 3174 produced directionally similar, but temporally disparate, haemodynamic effects [7].
• The potent and selective orally active ANG II receptor antagonist losartan (DuP 753) enhanced the retentions in an inhibitory (passive) avoidance test after scopolamine amnesia [8].
• In summary, the results of this open-label, uncontrolled study suggest that chronic treatment with losartan may improve ventilatory efficiency and decrease plasma brain natriuretic peptide concentrations with the improvement of physical activity and left ventricular systolic function in patients with CHF [9].

High impact information on losartan

• Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy [3].
• In vivo treatment of Agtr1(+/+) mice with losartan reduced phagocytic capability of Agtr1(+/+) macrophages to a level comparable to that of Agtr1(-/-) macrophages [10].
• Administration of an AT1 receptor antagonist, losartan, also significantly increased cortical COX-2 mRNA expression and COX-2 immunoreactivity [11].
• The AT1 blocker, losartan, abolished apoptosis in stretched myocytes [12].
• Nine healthy men were studied after 1 wk of the angiotensin II type I receptor antagonist losartan (100 mg daily) or placebo, according to a double-blind randomized crossover design [13].

Chemical compound and disease context of losartan

• The vasodilator hydralazine and the AT1 receptor antagonist losartan had comparable effects to reverse angiotensin II-induced hypertension, but only losartan blocked the changes in body weight and in circulating IGF I and its binding proteins produced by angiotensin II [14].
• Differences in QT dispersion (a predictor for sudden death) were observed in a subgroup of patients in the ELITE heart failure study of losartan compared with captopril, and may explain improved survival with losartan [15].
• CONCLUSIONS: Unlike propranolol, long-term losartan administration does not significantly reduce HVPG in patients with cirrhosis treated after a variceal bleeding episode, and it caused hypotension and reduced GFR in patients with moderate liver failure [16].
• Effects of enalapril versus losartan on regression of volume overload-induced cardiac hypertrophy in rats [17].
• In conclusion, the beneficial natriuretic effects of low-dose losartan on erect posture - induced sodium retention in preascitic cirrhosis supports the suggestion that the pathophysiology of sodium retention in preascites is in part caused by an intrarenal tubular effect of Ang II in that posture [18].

Biological context of losartan

• An activator of renin gene expression, the angiotensin II type I receptor inhibitor, losartan, increased cGK II mRNA and protein three to fourfold in JG cells [19].
• In the present study the effects of losartan, a selective AT1 receptor antagonist, and PD 123319, a selective AT2 antagonist, on the cardiac baroreflex response to Ang II were investigated in conscious rabbits with chronically implanted arterial and venous catheters [20].
• Failure of losartan to control blood pressure in scleroderma renal crisis [21].
• We report a case of maternal exposure to the antihypertensive drug losartan during weeks 20-31 of pregnancy [22].
• Losartan reduces hematocrit in patients with chronic obstructive pulmonary disease and secondary erythrocytosis [23].

Anatomical context of losartan

• After baseline hemodynamic measurements using balloon-tipped pulmonary artery and radial arterial catheters, patients were randomized to receive a single dose of placebo or 5, 10, 25, 75, or 150 mg losartan in a double-blind, sequential fashion [24].
• Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition [25].
• The role of tissue RAS was assessed by incubating isolated carotid arteries with an angiotensin-converting enzyme inhibitor (ACE I; lisinopril, 10(-6) mol/L) or with a specific antagonist of angiotensin II AT1 receptors (AT1A; losartan, 10(-6) mol/L) [26].
• Rat smooth muscle cells treated with Ang II exhibited a dose-dependent increase in MCP-1 mRNA accumulation that was prevented by the AT1 receptor antagonist losartan [27].
• Competitive radioligand binding studies showed that cardiac fibroblasts have a single class of high-affinity (IC50, 1.0 nM) angiotensin II binding sites (Bmax, 778 fmol/mg protein) that are sensitive to the competitive nonpeptide AT1 receptor antagonist losartan (IC50, 13 nM) [28].

Associations of losartan with other chemical compounds

• Intrarenal administration of angiotensin II receptor type 1 (AT1) receptor antagonists losartan or EXP-3174 simultaneously with ANG II caused dose-dependent inhibition of ANG II responses [29].
• Neither losartan nor PD123177 alone significantly inhibited ANG II-evoked NO release, and when cells were stimulated with ANG II in the presence of losartan (10 microM) and PD123177 (10 microM) in combination, NO release was significantly inhibited (P < 0.05) [30].
• This inhibitory effect of AII on IRS-1/PI 3-kinase association was blocked by the AII receptor antagonist saralasin, but not by AT1 antagonist losartan or AT2 antagonist PD123319 [31].
• METHODS: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks [32].
• The primary endpoint occurred in 103 patients assigned losartan (n=586) and 139 assigned atenolol (n=609); relative risk 0.76 (95% CI 0.58-.98), p=0.31 [33].

Gene context of losartan

• Treatment with either losartan (25 mg x kg(-1) x d(-1)) or hydralazine (15 mg x kg(-1) x d(-1)), both of which prevented the Ang II-induced hypertension, blocked HO-1 mRNA upregulation [34].
• Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan [35].
• On this basis we hypothesized that BLEO-induced apoptosis and lung fibrosis in mice would be inhibited by the AT1 antagonist losartan (LOS) or by targeted deletion of the AT1 gene [36].
• Treatment of AT1 receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in (3)H-glucosamine/(35)S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan [37].
• The AngII receptor (AT1) antagonist Losartan (10 microM) prevented AngII-induced, but not stretch-induced, VEGF protein secretion (AngII 1.7+/-0.3, AngII + Losartan 1.0+/-0.1, P<0.05; stretch 2.4+/-0.4, stretch + Losartan 2.6+/-0.5) [38].

Analytical, diagnostic and therapeutic context of losartan

• METHODS: A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years [1].
• The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005) [1].
• This was completely abrogated by simultaneous losartan perfusion [39].
• Losartan and renal transplantation [40].
• To examine the importance of AT1 receptor expression, another group of isolated rat hearts (n=5) was perfused with buffer containing losartan (10(-5) mol/L) and subjected to ischemia followed by reperfusion [41].

References