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BACKGROUND: The role of kinins in the cardioprotective effects of ACE inhibitors remains controversial. METHODS AND RESULTS: Right ventricular pressure overload in rabbits was produced by pulmonary artery banding for 21 days. Rabbits were untreated, or they received the ACE inhibitor ramipril with or without bradykinin B(1) and B(2) receptor blockers or the angiotensin (Ang) II type I (AT(1)) receptor blocker losartan. Pulmonary artery banding caused right ventricular hypertrophy, depressed papillary muscle contractility, and loss of Ang II contractile effects because of a signaling defect downstream of AT(1) receptors. Paradoxically, AT(1) receptor density and G protein alpha subunits alphaq and alphai1/2 increased. Inotropic responsiveness to the alpha-receptor agonist phenylephrine was normal. Ramipril preserved cardiac contractility, but this effect was attenuated by simultaneous use of kinin receptor blockers. Ramipril also maintained responsiveness to Ang II and prevented AT(1) receptor and G protein upregulation. The simultaneous use of a kinin receptor blocker attenuated but did not prevent upregulation in the AT(1) receptor and G protein. Losartan had no effect on baseline contractility, but it maintained cardiac inotropic responsiveness to Ang II, prevented upregulation of AT(1) receptors, but did not modify G protein upregulation. CONCLUSIONS: Pressure overload of the right ventricle decreases contractility, uncouples AT(1) receptors to downstream signaling pathways, and changes the expression of components of the AT(1) receptor signaling pathway. Ramipril attenuates these effects via kinins. Interventions that prevent local increases in Ang II or block AT(1) receptors also prevent decreased responsiveness of the AT(1) receptor in this model.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11514383&dopt=Abstract

rug.ac.be

A capillary electrophoresis method was developed for the simultaneous determination of hydrochlorothiazide and several angiotensin-converting enzyme (ACE) inhibitors: enalapril, lisinopril, quinapril, fosinopril, ramipril, and cilazapril. The most critical parameter is the pH of the running buffer. Separation was performed on a fused-silica capillary (52 cm total length x 75 microm I.D.) using a sodium phosphate buffer (pH 7.25; 100 mM). The method was successfully applied to the quantitative determination of these compounds in their corresponding pharmaceutical formulation. The method was validated in terms of linearity of response, reproducibility and accuracy.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11521895&dopt=Abstract

yahoo.com

AIMS: The MICRO-HOPE substudy demonstrated that when ramipril treatment was added to people with Type 2 diabetes and additional cardiovascular risk factors cardiovascular events were reduced by 25% in 4.5 years. We wished to determine the proportion of people with Type 2 diabetes and additional cardiovascular risk factors registered with a hospital diabetes service. METHODS: Non-proteinuric people (n = 1370) with Type 2 diabetes identified on our diabetes register were subject to analysis. Anticipated reductions in cardiovascular events due to ramipril treatment were based on reductions observed in the MICRO-HOPE substudy. RESULTS: Non-proteinuric people (n = 1075 (78%)) with Type 2 diabetes had at least one additional cardiovascular risk factor. Twenty-nine percent were already taking an angiotensin-converting enzyme inhibitor. The remaining 764 patients were similar to ramipril-treated participants in the MICRO-HOPE substudy. Treatment with ramipril for 4.5 years would be anticipated to reduce cardiovascular deaths by 26, revascularization procedures by 19 and admissions for myocardial infarction and stroke by 18 and 26, respectively. CONCLUSIONS: Of non-proteinuric people with Type 2 diabetes, 78% have additional cardiovascular risk factors. Only a small proportion currently receive treatment with an angiotensin-converting enzyme inhibitor. The incidence of cardiovascular events could be reduced if more patients were treated with ramipril and other cardiovascular risk factors were addressed.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11553206&dopt=Abstract













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