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Losartan Treatment (losartan + treatment)
Selected Abstracts11b-hydroxysteroid dehydrogenase activity in proteinuric patients and the effect of angiotensin-II receptor blockadeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2002M. N. Kerstens Abstract Background It has been suggested that an altered setpoint of the 11,HSD-mediated cortisol to cortisone interconversion towards cortisol contributes to sodium retention in nephrotic syndrome patients. We studied the parameters of 11,HSD activity in proteinuric patients, in particular its activity at the kidney level. We also studied the effect of angiotensin-II receptor blockade on the parameters of 11,HSD activity. Materials and methods Serum cortisol/cortisone ratio and the urinary ratios of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydrocortisone [(THF + allo-THF)/THE] and of urinary free cortisol/free cortisone (UFF/UFE) were measured in eight proteinuric patients and compared with eight matched, healthy subjects. Patients were subsequently studied after 4 weeks' treatment with losartan 50 mg day,1 and placebo, respectively. Results No significant differences between the proteinuric patients and the healthy subjects were observed in the serum cortisol, serum cortisone, serum cortisol to cortisone ratio, or in the urinary excretions of THF, allo-THF, THE, sum of cortisol metabolites, or the (THF + allo-THF)/THE ratio. Urinary free cortisol excretion and the UFF/UFE ratio were lower in the proteinuric patients than in the healthy subjects (56 ± 21 vs. 85 ± 24 pmol min,1, P < 0·05, and 0·39 ± 0·07 vs. 0·63 ± 0·28, P < 0·05, respectively). Mean arterial pressure and proteinuria were reduced significantly during losartan treatment, but without concomitant changes in peripheral cortisol metabolism. Conclusions Increased renal inactivation of cortisol in proteinuric patients does not support the contention that altered 11,HSD activity contributes to sodium retention in patients with nephrotic syndrome. Losartan 50 mg d.d. reduces mean arterial pressure and proteinuria, but does not exert a significant effect on the cortisol to cortisone interconversion. [source] Angiotensin II Is a Critical Mediator of Prazosin-Induced Angiogenesis in Skeletal MuscleMICROCIRCULATION, Issue 6 2007Matthew C. Petersen ABSTRACT Objective: The purpose of this study was to determine whether a high-salt diet modulates physiological angiogenesis in skeletal muscle by altering angiotensin II (ANGII) and vascular endothelial growth factor (VEGF) levels. Methods: Sprague-Dawley rats were placed on a control diet (0.4% NaCl by weight) or high-salt diet (4.0% NaCl) prior to treatment with the vasodilator prazosin in the drinking water. In addition, a group of animals fed high salt were infused intravenously with ANGII at a low dose to prevent ANGII suppression by high salt, and a group of rats fed control diet were treated with the angiotensin II type I (AT1) receptor blocker losartan and prazosin. Results: Prazosin induced significant angiogenesis in the tibialis anterior muscle after 1 week of treatment. High-salt-fed rats demonstrated a complete inhibition of this angiogenic response. Maintenance of ANGII levels restored prazosin-induced angiogenesis in animals fed a high-salt diet. In addition, losartan treatment blocked prazosin-induced angiogenesis in animals on a control diet. Western blot analysis indicated that prazosin-induced angiogenesis was independent of changes in muscle levels of VEGF. Conclusions: This study demonstrates an inhibitory effect of high salt intake on prazosin-induced angiogenesis. Further, these results indicate that ANGII acting through the AT1 receptor is a critical pathway in this model of angiogenesis. [source] Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndromeBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2009HH Clarice Yang Background and purpose:, During development of thoracic aortic aneurysms in a mouse model of Marfan syndrome, upregulation of matrix metalloproteinase (MMP)-2 and -9 was accompanied by compromised aortic constriction and endothelium-dependent relaxation. Losartan has been proposed for the prevention of thoracic aortic aneurysm. We hypothesized that losartan would suppress MMP-2/-9 activation and improve aortic vasomotor function in this model. Experimental approach:, A well-characterized mouse model of Marfan syndrome (Fbn1C1039G/+) was used. Starting at 6 weeks old, Marfan mice were untreated or given losartan (0.6 g·L,1 in drinking water, n= 30). The littermate Fbn1+/+ mice served as control. Thoracic aortas were studied at 3, 6 and 9 months by histology and by contractility assays in isolated segments in vitro. Key results:, Losartan improved elastic fibre organization and increased aortic breaking stress. Losartan reduced the activity and protein expression of MMP-2 and MMP-9 at all ages. Aortic constriction in response to membrane depolarization or phenylephrine was increased by losartan at 3 and 9 months by 100,200%. Active force of aortic smooth muscle was also increased at 6 and 9 months. Acetylcholine-induced endothelium-dependent relaxation was improved by 30% after 3 months of losartan treatment, but such improvement disappeared with longer duration of treatment, accompanied by reduced phosphorylation of endothelial nitric oxide (NO) synthaseSer1177, AktThr308 and AktSer473, compared with the control. Conclusions and implications:, Losartan improved the contractile function of aorta and reduced MMP activation. However, the endothelial NO pathway remained suppressed in the thoracic aorta during losartan treatment, which might limit its long-term benefits in Marfan syndrome. [source] CHRONIC EFFECTS OF ANGIOTENSIN II and AT1 RECEPTOR ANTAGONISTS IN SUBFORNICAL ORGAN-LESIONED RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005John P Collister SUMMARY 1.,Angiotensin (Ang) II is known to exert some of its effects centrally via circumventricular organs. These unique central nervous system areas lack the normal blood,brain barrier and, therefore, allow peptide hormones access to the brain. Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII. We hypothesized that the SFO is a central site involved in the chronic hypotensive effects of endogenous AT1 receptor blockade, as well as the chronic hypertensive effects of exogenously administered AngII. 2.,In order to test these hypotheses, SFO-lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers for intravenous administration of losartan or AngII and continuous measurement of blood pressure and heart rate. Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per min) for 10 days. 3.,By day 4 of losartan treatment, arterial pressure had decreased 24 ± 2 and 18 ± 2 mmHg in sham (n = 9) and SFOx (n = 10) rats, respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had increased 12 ± 3 mmHg in sham rats (n = 9), but only by 4 ± 1 mmHg in SFOx rats (n = 9). In each treatment group, these attenuated pressure responses in SFOx rats continued through day 10 of treatment. 4.,These results support the hypotheses that the SFO plays a role in both the hypotensive effects of chronic AT1 receptor blockade and the chronic hypertensive phase of exogenously administered AngII. [source] | ||||||||||