Disease relevance of Ramiprilat

• Eight dogs received a continuous intracoronary infusion of HOE 140 [0.5 ng/(mL.min) IC] during ischemia and reperfusion (group 3), and in 8 dogs HOE 140 was infused continuously during ischemia and reperfusion, starting 45 minutes before the administration of ramiprilat (group 4) [1].
• Aspirin does not prevent the attenuation of myocardial stunning by the ACE inhibitor ramiprilat [2].
• The objective of this investigation was to determine the role of nitric oxide synthase in the action of the angiotensin-converting enzyme inhibitor, ramiprilat, to reduce myocardial ischemia/reperfusion injury [3].
• Exogenous BK at a nanomolar concentration was incubated alone, in the presence of an ACE inhibitor (ramiprilat, 36 nM), or in the presence of a VPI (omapatrilat, 61 nM) with left ventricular membranes prepared from normal donor hearts (n = 7), and hearts from patients with an ischemic (n = 11) or dilated (n = 12) cardiomyopathy (DCM) [4].
• Reduction of myocardial infarct size by ramiprilat is independent of angiotensin II synthesis inhibition [5].

High impact information on Ramiprilat

• In myocardium, kininogen (10 micrograms/mL) and captopril, enalaprilat, or ramiprilat (10(-4) mol/L) reduced cardiac O2 consumption by 41 +/- 2%, 19 +/- 3%, 25 +/- 2%, and 35 +/- 2%, respectively [6].
• CONCLUSIONS: Other than decreasing angiotensin II production, acute ramiprilat-induced vasodilation in canine coronary conductance arteries is mediated in part by nitric oxide [7].
• Felodipine, but not ramiprilat, concentration-dependently inhibited cytokine-induced NO production and NO synthase (NOS) mRNA induction [8].
• This study aimed to determine the density of vascular beta-adrenergic receptors in cultured endothelial cells and to study the regulation of endothelial receptors after exposure to catecholamines and the ACE inhibitors, lisinopril and ramiprilat [9].
• The angiotensin converting enzyme (ACE) inhibitors, moexiprilat and ramiprilat, relaxed preconstricted endothelium-intact bovine coronary artery rings and enhanced the relaxant response to bradykinin [10].

Chemical compound and disease context of Ramiprilat

• The attenuation of myocardial stunning by the ACE inhibitor ramiprilat is prevented by cyclooxygenase inhibition with indomethacin [2].
• Therefore, we examined the effects of inhibitors of angiotensin-converting enzyme (ramiprilat), EP24.11 (cFP-F-pAB), and EP24.15 (cFP-AAF-pAB) in a chronic model of myocardial ischemia/reperfusion injury [11].
• Also, when isolated neonatal rat cardiomyocytes were exposed to hypoxia/reoxygenation, ramiprilat (100 mumol/L) and bradykinin (10 nmol/L) improved cell viability (approximately 60%), and the protective effect of both agents was reversed by administration of HOE 140 (10 mumol/L) [12].
• Differential effects of saralasin and ramiprilat, the inhibitors of renin-angiotensin system, on cerulein-induced acute pancreatitis [13].
• In an open trial, the pharmacokinetics of ramipril and its active metabolite ramiprilat were studied in 23 hypertensive patients with various degrees of renal insufficiency [14].

Biological context of Ramiprilat

• The nitric oxide synthesis inhibitor increased blood pressure in spontaneously hypertensive rats and attenuated the hypotensive effect of captopril, ramiprilat, and DuP 753, but it did not impede the hypotensive effect of sodium nitroprusside [15].
• The kinetics of the steady-state inhibition of angiotension I-converting enzyme (EC 3.4.15.1) at 25 degrees C and 37 degrees C with enalaprilat and ramiprilat can be simulated, assuming only one inhibitor-binding site, consistent with a 1:1 stoichiometry if the protein concentration was determined by amino acid analysis [16].
• In the therapeutic concentration range, protein binding of ramipril and ramiprilat is 73 and 56%, respectively [17].
• The present study therefore investigated whether aspirin in dosages sufficient to inhibit platelet aggregation interferes with the attenuation of myocardial stunning by ramiprilat [2].
• The ramiprilat-resistant kininase activity was for the most part inhibited by the selective APP inhibitor apstatin (IC50 0.9 microM) [18].

Anatomical context of Ramiprilat

• The supernatant of endothelial cells, incubated with ramiprilat (0.3 microM) for 15 minutes, elicited a significant nitric oxide release (as assessed by a guanylyl cyclase assay) in untreated endothelial cells used as detector tissue [19].
• Lisinopril and ramiprilat protection of the vascular endothelium against free radical-induced functional injury [20].
• Kinin degradation pathways of intact PC12 cells were characterized by identification of the kinin fragments generated from tritiated bradykinin either in the absence or presence of the angiotensin I-converting enzyme inhibitor ramiprilat [21].
• CONCLUSION: In our study we demonstrated for the first time that ramiprilat reduced expression of AT1R in monocytes and endothelial cells [22].
• The decrease in angiotensin converting enzyme activity persisted in the brush border membrane after elimination of residual ramiprilat with EGTA [23].

Associations of Ramiprilat with other chemical compounds

• The most potent converting enzyme inhibitors toward aminopeptidase P were the carboxylalkyl compounds, cilazaprilat, enalaprilat, and ramiprilat (I50 values of 3-12 microM) [24].
• These data suggest a contribution of endogenous kinins and nitric oxide to the acute antihypertensive effect of captopril and ramiprilat in spontaneously hypertensive rats and of nitric oxide to the hypotensive effect of DuP 753 [15].
• After desensitization with BK, but not FR190997, an additional application of ramiprilat provoked a B(2) receptor-mediated vasodilation [25].
• RESULTS: Whereas ramiprilat (0.5-4 micrograms/kg/min intra-arterially) and EXP 3174 (0.5-4 micrograms/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 micrograms/kg/min, captopril (1-8 micrograms/kg/min intra-arterially) did not change blood pressure except for a slight effect with the two higher doses [26].
• OBJECTIVES: Our aim was to investigate the potential therapeutic role of endothelial nitric oxide synthase (eNOS) in the modulation of cardiac O(2) consumption induced by the angiotensin converting enzyme (ACE) inhibitor ramiprilat and amlodipine [27].

Gene context of Ramiprilat

• Studies with the converting enzyme inhibitor ramiprilat and the bradykinin receptor antagonist icatibant indicate that bradykinin mediates, at least partly, diuretic NPY effects [28].
• In an endothelial cell line stably expressing human somatic ACE, ramiprilat increased COX-2 promoter activity, an effect not observed in ACE-deficient cells or cells expressing a nonphosphorylatable ACE mutant (S1270A) [29].
• The ramiprilat-induced, ACE-dependent increase in COX-2 expression and promoter activity (both 1.5- to 2-fold greater than control) was prevented by the inhibition of JNK [29].
• However, B2 receptor-deficient mice (B2-/-) unexpectedly responded to IPC or ramiprilat like WT mice [30].
• Ramiprilat also reduced infarct size by 29% in WT, but in TK-/- its effect was completely suppressed [30].

Analytical, diagnostic and therapeutic context of Ramiprilat

• Ramiprilat increased both epicardial cross-sectional area and coronary blood flow velocity, resulting in an increase in absolute coronary blood flow [7].
• Perfusion with ramiprilat increased the bradykinin concentration to 2.8 +/- 0.3 ng ml-1 perfusate g-1 wet weight [31].
• The pressor effect produced by bilateral microinjection of Ang I into the RVLM of anesthetized rats was not significantly altered by DuP 753 or by the ACE inhibitor ramiprilat [32].
• The developed LC-MS procedures were applied for the determination of the pharmacokinetic parameters of ramipril and ramiprilat following a single oral administration of 10mg ramipril tablets in 18 Chinese healthy male volunteers [33].
• (c) Acute myocardial infarction: Ramiprilat (40 ng/kg/min) was infused for 6 h into the left coronary artery of anesthetized dogs with a ligation of the descending branch of this artery [34].

References