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Olmesartan medoxomil : a review of its use in the management of hypertension.
Drugs. 2008; 68(9): 1239-72
Scott LJ, McCormack PL
Olmesartan medoxomil (Olmetec((R)), Benicar((R))) is an angiotensin II type 1 (AT(1)) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system, which plays a key role in the pathogenesis of hypertension. Oral olmesartan medoxomil 10-40 mg once daily is recommended for the treatment of adult patients with hypertension. In those with inadequate BP control using monotherapy, fixed-dose olmesartan medoxomil/hydrochlorothiazide (HCTZ) [Olmetec plus((R)), Benicar-HCT((R))] combination therapy may be initiated.Extensive clinical evidence from several large well designed trials and the clinical practice setting has confirmed the antihypertensive efficacy and good tolerability profile of oral olmesartan medoxomil, as monotherapy or in combination with HCTZ, in patients with hypertension, including elderly patients with isolated systolic hypertension (ISH). Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 4 hours of this period. In clinical trials, olmesartan medoxomil monotherapy provided better antihypertensive efficacy than losartan, candesartan cilexetil or irbesartan monotherapy, and was at least as effective as valsartan treatment, with a faster onset of action than other ARBs in terms of reductions from baseline in diastolic BP (DBP) and, in most instances, systolic BP (SBP). Combination therapy with olmesartan medoxomil plus HCTZ was superior to that with benazepril plus amlodipine, as effective as that with losartan plus HCTZ, noninferior to that with atenolol plus HCTZ, but less effective than that with telmisartan plus HCTZ, in individual trials. Data from ongoing clinical outcome trials are required to more fully determine the relative position of olmesartan medoxomil therapy in the management of hypertension. In the meantime, the consistent antihypertensive efficacy during the entire 24-hour dosage interval and good tolerability profile of olmesartan medoxomil, with or without HCTZ, make it a valuable option for the treatment of adult patients with hypertension, including the elderly.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2008 Apr; 28(4): 360-3
Guo DZ, Wang YH, Chen ZQ
OBJECTIVE: To observe the clinical effect of combined treatment with safflor yellow powder injection and benazepril in treating patients with diabetic nephropathy (DN). METHODS: Seventy-six patients with DN were randomly assigned to the treatment group (39 cases) and the control group (37 cases). Conventional treatment for lowering blood glucose was given to both groups, but to the control group 10 mg benazepril was given orally once a day additionally, while to those in the treatment group the same dosage of benazepril po. and 150 mg/d of safflor yellow powder injection by adding in 250 mL 0.9% normal saline for intravenous dripping. The therapeutic course for them all was 15 days, and all patients received two courses with an interval of 5 days. Changes of clinical symptoms, urinary albumin excretion rate (UAER), blood and urinary levels of beta2 -microglobulin (beta2 -MG), urinary level of alpha1-microglobulin (alpha1 -MG), D-dimer (D-D) and plasma fibrinogen (FIB) were observed. RESULTS: The total effective rate in the treatment group was higher than that in the control group (84.62% vs 59.45 %, P < 0.05). The total score of syndrome in the treatment group was lower than that in the control group (P < 0.05). Levels of UAER, 132-MG in serum and in urine, alpha1-MG in urine were decreased significantly after after 2 courses of treatment in both groups, showing significant difference as compared with before treatment (P < 0.05 or P
J Vet Intern Med. 2008 Jun 4;
O'Grady MR, Minors SL, O'Sullivan ML, Horne R
Background: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. Hypothesis: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. Animals: Sixteen Doberman Pinschers in CHF caused by DCM. Methods: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). Results: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. Conclusions and Clinical Importance: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.
J Vet Med Sci. 2008 May; 70(5): 455-60
Mishina M, Watanabe T
In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre- and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (p
Ethn Dis. 2008; 18(2): 204-9
Dickson M, Plauschinat CA
OBJECTIVE: To assess compliance with antihypertensive therapy and healthcare utilization among African American and White Medicaid recipients who are receiving fixed-dose combination amlodipine besylate/benazepril HCl or a dihydropyridine calcium channel blocker plus an angiotensin-converting enzyme inhibitor prescribed as separate agents (free-combination). DESIGN: Longitudinal, retrospective, cohort analysis of South Carolina Medicaid claims for the years 1997 through 2002. Followup was 12 months from the index date, defined as the first prescription dispensing date for a study drug. SETTING AND PARTICIPANTS: South Carolina Medicaid beneficiaries receiving fixed-dose (n=3363) and free-combination (n=713) therapy, including 3016 African Americans and 1060 White patients. MAIN OUTCOME MEASURES: Compliance was defined as the total days' supply of drug (excluding last prescription fill) divided by the length of followup; healthcare utilization included cost and number of claims associated with ambulatory services, hospital care, and prescription drugs. RESULTS: The cohort (N=4076) was 74.0% African American; mean age was 62.2 years. Compliance was significantly greater in patients who received fixed-dose therapy than in those who received free-combination therapy (58.6% vs 48.1%; P
Naunyn Schmiedebergs Arch Pharmacol. 2008 May 24;
He H, Shi M, Yang X, Zeng X, Wu L, Li L
The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.
J Vet Intern Med. 2008 May 8;
Pouchelon JL, Jamet N, Gouni V, Tissier R, Serres F, Carlos Sampedrano C, Castaignet M, Lefebvre HP, Chetboul V
Background: Angiotensin-converting enzyme inhibitors (ACEIs) improve quality of life and extend the life span of dogs with naturally acquired ISACHC class II-III congestive heart failure (CHF). However, their effects on asymptomatic heart disease remain controversial. Hypothesis: Benazepril (BNZ), an ACEI, could have beneficial effects at the asymptomatic stage of degenerative mitral valve disease (MVD). Animals: Dogs with ISACHC class Ia MVD and moderate-to-severe mitral regurgitation (MR) assessed by the color Doppler mapping technique at entry (Day 0) were retrospectively included. Methods: Dogs were assigned to the treated group (BNZ group) if they received BNZ (and no other cardiac medication) from Day 0 or to the untreated group (UT group) if they did not receive any cardioactive treatment until occurrence of CHF. Results: A total of 141 dogs were included in the study, 66 in the BNZ group (dosage: 0.30 +/- 0.13 mg/kg) and 75 in the UT group. In the population (n = 93) including all breeds except Cavalier (CKC) and King Charles Spaniels (KC), median survival time to all causes of death in the BNZ group (n = 34, 3.3 years) was significantly longer than in the UT group (n = 59, 1.9 years) as was time to cardiac event (P < .05). Conversely, no effect of the BNZ treatment was observed in the CKC and KC population. Conclusions and Clinical Relevance: BNZ had beneficial effects in asymptomatic dogs other than CKC and KC affected by MVD with moderate-to-severe MR. Breed distribution should be taken into account for interpretation of clinical trials performed in dogs with cardiac disease.
Zhong Xi Yi Jie He Xue Bao. 2008 May; 6(5): 512-6
Chen JH, Sun W, Zhou D, Gao K, He WM, Liu L
Objective: To explore the mechanisms of the beneficial effects of Dahuang Zhechong Pill (DHZCP), a Chinese patent herbal medicine, in treatment of chronic renal disease, and to investigate the effects of DHZCP on the expressions of renal tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) mRNAs in rats with adriamycin-induced glomerulosclerosis. Methods: Focal segmental glomerulosclerosis and diffuse mesangial proliferation were induced in rats by combined procedures, including unilateral nephrectomy, intravenous injection of adriamycin and giving high-fat foods. The rats were randomly divided into untreated group, benazepril-treated group and DHZCP-treated group. Another 6 rats were sham-operated as control group. After 12-week treatment, rats were sacrificed, reverse transcription polymerase chain reaction (RT-PCR) method and computerized image analytical technique were used to determine the expressions of TIMP-1 and PAI-1 mRNAs. Results: Compared with the untreated group, the ratios of TIMP-1/beta-actin and PAI-1/beta-actin of the DHZCP-treated group were decreased, suggesting that DHZCP could down-regulate the expressions of TIMP-1 and PAI-1 mRNAs (P
J Renin Angiotensin Aldosterone Syst. 2008 Mar; 9(1): 1-9
Gojanovic B, Feihl F, Liaudet L, Waeber B
Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists (CAs) and blockers of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (ARBs)] are widely used today to initiate antihypertensive treatment but, when given as monotherapy, do not suffice in most patients to normalise blood pressure (BP). Combining a CA and either an ACE-inhibitor or an ARB considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. Several fixed-dose combinations are available (CA + ACE-inhibitors: amlodipine + benazepril, felodipine + ramipril, verapamil + trandolapril; CA + ARB: amlodipine + valsartan). They are expected not only to improve BP control, but also to facilitate long-term adherence with antihypertensive therapy, thereby providing maximal protection against the cardiovascular and renal damage caused by high BP.
Nephrol Dial Transplant. 2008 Apr 5;
Zhu S, Liu Y, Wang L, Meng QH
BACKGROUND: Evidence suggests that transforming growth factor-beta1 (TGF-beta(1)) is associated with target organ damage in hypertension. This study aimed to investigate the relationship between TGF-beta(1) levels and kidney damage and renoprotective effects of angiotensin-converting enzyme inhibitor and/or angiotensin II type 1 receptor blocker in patients with essential hypertension (EH). METHODS: A total of 156 patients with EH were enrolled and grouped according to albumin-to-creatinine ratio (ACR). Of these, 90 patients with EH underwent a 12-week antihypertensive trial with administration of benazepril, valsartan or both. Serum TGF-beta(1), plasma angiotensin (Ang) II and urinary albumin were quantified by immunoassays. RESULTS: Serum TGF-beta1, plasma Ang II and ACR were highly elevated in patients with EH (P < 0.01). There was a positive correlation between serum TGF-beta1 levels and ACR (r = 0.53, P < 0.01). Significant decreases in TGF beta1 and ACR were obtained in all groups at the end of 12-week antihypertensive therapy compared to the baseline values, with the combined group to a greater extent (P < 0.01). Plasma Ang II levels were significantly decreased in the benazepril group but increased in the valsartan group (P < 0.05) while no significant change was observed in the combined group. CONCLUSIONS: TGF-beta(1) is highly elevated and strongly associated with urinary albumin excretion in patients with EH. Treatment with benazepril or valsartan attenuates serum TGF-beta(1) levels and microalbuminuria with the combined therapy receiving the greater effect. TGF-beta(1) could be a potential surrogate marker in monitoring the development and progression of kidney damage in EH.