Drugs online research references
Eur J Pharmacol. 1992 Mar 17;213(1):137-9.
The effect of hydrochlorothiazide on the enhanced coughing associated with treatment with enalapril.
Kamei J, Kasuya Y.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
The effect of hydrochlorothiazide, a diuretic which is used in the treatment not only of edema but also of hypertension, on coughs associated with treatment with enalapril was studied in guinea pigs. Chronic treatment with enalapril markedly and dose dependently enhanced the number of capsaicin-induced coughs. However, chronic treatment with hydrochlorothiazide significantly reduced the number of coughs associated with enalapril treatment, also in a dose-dependent manner. These results suggest that diuretics might be used to reduce the coughing associated with treatment with inhibitors of angiotensin-converting enzyme in patients with hypertension.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1499649&dopt=Abstract
Nephrol Dial Transplant. 1997 Mar;12(3):456-64.
Enalaprilat inhibits hydrogen peroxide production by murine mesangial cells exposed to high glucose concentrations.
Ruiz-Munoz LM, Vidal-Vanaclocha F, Lampreabe I.
Department of Nephrology, Cruces Hospital, Vizcaya, Spain.
BACKGROUND: Oxidative stress is considered to play a role in the pathogenesis of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors are hypotensive drugs with a well-known effect in preventing the progression of chronic renal failure. Their mechanism of action is not clearly established. METHODS: The effect of enalaprilat on hydrogen peroxide (H2O2) production by cultured murine mesangial cells exposed to 5.5 (basal condition), 30 and 50 mM glucose concentrations was examined over 8 h. A fluorimetric method quantifying, in arbitrary units, the intracellular dichlorofluorescein (DCFH) oxidation to the highly fluorescent compound 2'7'dichlorofluorescein (DCF) from the non-fluorescent probe dichlorofluorescein-diacetate (DCFH-DA) was employed (a method not previously reported for cultured mesangial cells). Experiments were repeated three times in quadruplicate wells. RESULTS: H2O2 production by mesangial cells exposed to 50 mM glucose was significantly increased after 1 h, compared to cells exposed to 5.5 and 30 mM glucose. This observation was not reproduced with 50 mM mannitol. Addition of 100 ng/ml enalaprilat to cells with 50 mM glucose significantly inhibited H2O2 production during the 8 h of the assay. This response was similar to that obtained with 100 ng/ml catalase. Increasing enalaprilat concentrations (10, 50 and 100 ng/ml) also significantly decreased the constitutive H2O2 generation in the presence of 5.5 mM glucose. Angiotensin II and saralasin, both at 1 microM, did not modify H2O2 production by cells exposed to 5.5 mM glucose. In contrast, 1 microM staurosporine, a protein kinase C (PKC) antagonist, significantly decreased H2O2 generation in the presence of 50 mM glucose. CONCLUSION: Enalaprilat has an antioxidant effect in cultured mesangial cells. This action is not linked to ACE inhibition, but may be related to an inhibition of the PKC system.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9075124&dopt=Abstract
J Pharmacol Exp Ther. 1991 Apr;257(1):294-301.
Esterases for enalapril hydrolysis are concentrated in the perihepatic venous region of the rat liver.
Pang KS, Barker F 3rd, Cherry WF, Goresky CA.
Faculty of Pharmacy, University of Toronto, Montreal, Canada.
Perfusion of substrate via only the hepatic artery with simultaneous substrate-free perfusion of portal vein or hepatic vein [hepatic artery portal vein-hepatic artery hepatic vein] was used to examine the enzymic distribution of carboxylesterases towards the hydrolysis of enalapril to enalaprilat in the perfused rat liver preparation. In this single-pass method, [14C]enalapril was delivered by the hepatic artery at 2 ml/min into the liver, whereas drug-free perfusate entered the portal vein or hepatic vein at 10 ml/min for HAPV and HAHV perfusions, respectively. During steady state, a multiple indicator dose of 51Cr-labeled red blood cells (vascular marker), [58Co]EDTA (interstitial space marker, which behaves similarly to labeled tracer sucrose), and 3H2O was given into the hepatic artery. Labeled enalapril and the reference indicators entering via the hepatic artery will reach virtually all sinusoidal spaces during HAPV, and will be confined to the peripheral region during HAHV. By defining the steady-state extraction ratios of enalapril (Etot) and segregating the components of biliary excretion and metabolism, and by assessing the intracellular water spaces and the corresponding transit times during HPAV and HAHV, the metabolic sequestration rate constant (metabolic intrinsic clearance per unit accessible cell water space) for the periportal region/whole liver (HAHV/HAPV) was 0.344. The data suggest that the carboxylesterase activity for enalapril conversion to enalaprilat is primarily localized in the perihepatic venous region of the rat liver.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1850468&dopt=Abstract
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