Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new vasotec research articles will be listed here shortly after becoming available to us.
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Medical research on vasotec
Clin Ter. 2008 May-Jun; 159(3): 151-4
Morano S, Cipriani R, Santangelo C, Fallarino M, Carnovale A, Mandosi E, Gatti A, Sensi M, Di Mario U
Aims. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor-1 (AT-1) antagonists are used in the treatment of proteinuria of diabetic nephropathy. One of the major pathogenic events in this condition is represented by the alteration of the extracellular matrix protein synthesis by glomerular epithelial cells. Materials and Methods. We evaluated the effects of the angiotensin converting enzyme inhibitor, Enalaprilat, and the AT-1 receptor antagonist, Losartan, on mRNA fibronectin and laminin synthesis by glomerular epithelial cells, in conditions mimicking hyperglycemia. Results. In high glucose conditions, Enalaprilat reduced significantly the mRNA expression of fibronectin (p 0.03), but not significantly that of laminin. Losartan addition to high glucose incubated cells reduced (-30%) mRNA expression of fibronectin, and significantly (p 0.05) the mRNA expression of laminin.Conclusions. In addition to the known hemodynamic effects, the improvement of renal function in diabetic patients treated with these compounds may also be due to a modulator effect on extracellular matrix content and composition. Clin Ter 2008; 159(3):151-154.
Biomed Chromatogr. 2008 May 27;
Hu W, Xu Y, Liu F, Liu A, Guo Q
A sensitive, specific and rapid high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was described and validated for the quantification of ambroxol in human plasma using enalaprilat as the internal standard (IS). Chromatographic separation was performed on a Lichrospher CN column with a mobile phase of methanol and water (containing 0.1% formic acid) (70:30, v/v). The total run time was 5.0 min for each sample. The analytes was detected by mass spectrometry with electrospray ionization source in positive selected reaction monitoring mode. The precursor-fragment ion reaction for ambroxol was m/z 378.9 --> 263.8, and for IS was m/z 349.0 --> 205.9. The linearity was established over the concentration range of 1.56-400.00 ng/mL. The inter-day and the intra-day precisions were all within 10%. A simple protein precipitation with methanol was adopted for sample preparation. The extraction recoveries of ambroxol and IS were higher than 90.80%. The validated method was successfully applied in pharmacokinetic study after oral administration of 90 mg ambroxol to 24 healthy volunteers. Copyright (c) 2008 John Wiley & Sons, Ltd.
Androgens stimulate proximal tubule transport.
Gend Med. 2008; 5 Suppl A: S114-20
Quigley R
BACKGROUND: Disrupting the enzyme cytochrome P4a14 in mice leads to hypertension, which is more severe in male than in female mice and appears to be due to androgen excess. Androgens are known to increase expression of angiotensinogen,but the effect of androgens on proximal tubule transport is unknown. OBJECTIVE: These studies aimed to determine the effect of androgens on proximal tubule transport. METHODS: Proximal tubules from knockout (KKO) and wild-ttype (WWT) (SSV/1129) mice were perfused in vitro. Volume resorption (JJ v ) was measured using 3 H-methoxy inulin as a volume marker. In separate experiments, male Sprague-Dawley rats were given dihydrotestosterone (DDHT) injections IP for 10 days. Proximal tubule transport was measured in this model using in vivo microperfusion. The renal expression of angiotensinogen was measured by Northern analysis, and brush border membrane protein abundance of the sodium-hhydrogen exchanger isoform 3 (NNHE3) was measured by Western blotting in the control and DHT-ttreated rats. RESULTS: Mean (SSE) Jv was significantly elevated in proximal tubules from KO mice compared with WT mice (11.11 [0.006] vs 0.77 [0.112] nL/mm . mm, respectively; P
Enalaprilat induced acute parotitis.
J Assoc Physicians India. 2008 Feb; 56: 128-9
Chauhan V, Negi RC, Sharma A, Gupta S, Mokta J, Verma B, Thakur S
Drug induced acute parotitis is a very uncommon complication reported with a few drugs only. There is no case of acute bilateral parotitis reported previously with i.v. enalaprilat. We present here a female patient who developed acute bilateral parotitis within minutes of i.v. enalaprilat injection and recovered within 24 hours of stopping the drug and with symptomatic treatment.
J Pharm Biomed Anal. 2008 Aug 5; 47(4-5): 934-7
Lima DM, Dos Santos LD, Lima EM
Stability of enalapril maleate formulations can be affected when the product is exposed to higher temperature and humidity, with the formation of two main degradation products: enalaprilat and a diketopiperazine derivative. In this work, stability and drug release profiles of 20mg enalapril maleate tablets (reference, generic and similar products) were evaluated. After 180 days of the accelerated stability testing, most products did not exhibit the specified amount of drug. Additionally, drug release profiles were markedly different from that of the reference product, mainly due to drug degradation. Changes in drug concentration and drug release profile of enalapril formulations are strong indicators of a compromised bioavailability, with possible interferences on the therapeutic response for this drug.
J Biomol Struct Dyn. 2008 Jun; 25(6): 599-608
Sramko M, Smiesko M, Remko M
Studies that allow computing values of aqueous proton dissociation constants (pKa), gas phase proton affinities, and the free energy of solvation have been performed for six members of angiotensin-I-converting enzyme (ACE) inhibitor family (captopril, enalaprilat, imidaprilat, ramiprilat, perindoprilat, and spiraprilat). Density functional theory (DFT) calculations using PBE1PBE functional on optimized molecular geometries have been carried out to investigate the thermodynamics of gas-phase protonation. The conductor-like polarizable continuum model (CPCM) solvation method at various levels of theory was applied to calculate the free energy of solvation for the ACE inhibitors and their respective anions. The CPCM solvation calculations were performed on both gas-phase and solvent-phase optimized structures. The combination of gas-phase and solvation energies according to the thermodynamic cycle enabled us to compute accurate pKa values for the all studied molecules.
Zhonghua Shao Shang Za Zhi. 2007 Oct; 23(5): 335-8
Zhang BQ, Huang YS, Zhang JP, Zhang DX, Dang YM, Wang G, Hu JY, Lei ZY, Xiao R
OBJECTIVE: To investigate the preventive and therapeutic effects of enalapril maleate(Enalaprilate) (E) on myocardial damage in early stage after burns. METHODS: A total of 60 SD rats were subjected to 30% TBSA III degree scald injury, and randomly divided into scald group (with conventional fluid transfusion after scald) and ENA group (with intraperitoneal injection of 1 mg/kg Enalaprilat after scald). Normal control consisted of 6 rats. Plasma levels of cTnI and CK-MB were determined in all the groups at 1, 3, 6, 12, 24 post-scald hours (PSH) by enzyme linked immunosorbent assay. The pathological changes in myocardium were observed at the same time-points. RESULTS: (1) The serum level of cTnI and CK-MB in scald group were significantly higher than that of normal controls at each time-point (P < 0.01). The serum level of cTnI and CK-MB in ENA group were (1.32 +/- 0.12 microg/L to 2.47 +/- 0.22 microg/L) and (438 +/- 68 U/L to 5569 +/- 322 U/L), respectively, which were obviously lower than those in B group (6.42 +/- 0.96 mcirog/L to 15.10 +/- 3.69 microg/L) and (2556 +/- 74 U/L to 8047 +/- 574 U/L, P < 0.05 or P < 0.01) at different time-points. (2) Compared with normal controls, cloudy swelling, stromal blood vessel dilatation and congestion imflammatory cell infiltration were observed in scald group, but these pathological changes were less marked in ENA group. CONCLUSION: Severe myocardial damage in rat occurred early after burns. Enalaprilat injection can markedly alleviate myocardial damage.
Life Sci. 2008 Apr 9; 82(15-16): 869-75
Tanaka M, Tokuyasu M, Matsui T, Matsumoto K
The goal of this study was to elucidate the structure-activity relationship for vasodilating peptides and their underlying mechanism. In this study, we synthesized 62 di- and tri-peptides having aromatic amino acid residues (Tyr, Trp and Phe). Among them, only 4 peptides (HW, WH, WL and WV) evoked an apparent vasodilating effect in 50 mM KCl-contracted aortic rings in the descending order of WH>HW>WL>WV; WH showed the vasodilating activity with an EC50 of 3.4 mM. Within our experimental results, it seems likely that Trp residue at the N-terminal would play a role in eliciting vasodilating effect. No appearance of vasodilating effect for stereoisomers of WH with D-configuration revealed that the vessel would recognize the L-configuration of WH. The presence of angiotensin I-converting enzyme (ACE) inhibitor (50 nM enalaprilat) did not affect the WH-induced vasodilating effect, though WH showed a slight ACE inhibitory activity (IC50: 93 microM). The effect was also observed in the endothelium-denuded aortic rings. In contrast, WH provoked a significant displacement to the right in the vasodilating curve in the presence of 30 nM verapamil, while no shift was observed in the presence of 2.5 nM nifedipine. These results indicate that WH, a vasodilating di-peptide, would exert a vasodilation via the suppression of Ca2+ influx into KCl-induced depolarized aortic rings. The present study also suggests that the binding site of WH to the Ca2+ channel may be competitive to that of phenylalkylamine-type voltage-gated L-type Ca2+ channel blocker.
Hypertension. 2008 Apr; 51(4): 1190-6
Pretorius M, van Guilder GP, Guzman RJ, Luther JM, Brown NJ
Angiotensin-converting enzyme inhibition potentiates basal and bradykinin-stimulated tissue-type plasminogen activator (t-PA) release to a greater extent in women than in men. This study tested the hypothesis that 17beta-estradiol enhances the effect of angiotensin-converting enzyme inhibition on t-PA release in young postmenopausal women. We conducted a double-blind, prospective, crossover study in 14 young postmenopausal women (mean age 48.2+/-2.3 years) who were randomized to receive 17beta-estradiol (1 mg/d) or matching placebo for 4 weeks. At the end of each treatment period, we measured the effect of intraarterial infusion of bradykinin, methacholine, and nitroprusside on forearm blood flow and net t-PA release, before and during intraarterial enalaprilat (0.33 microg/min/100 mL forearm volume). 17Beta-estradiol significantly reduced baseline venous plasminogen activator inhibitor-1 antigen (4.4+/-1.4 versus 10.4+/-2.5 ng/mL, P=0.001) and t-PA antigen (5.5+/-0.6 versus 7.5+/-1.3 ng/mL, P=0.022) compared with placebo. 17Beta-estradiol increased basal forearm vascular release of active t-PA compared with placebo (1.2+/-0.3 IU/mL/min versus 0.4+/-0.1 IU/mL/min respectively, P=0.032), without increasing t-PA antigen release (P=0.761). Enalaprilat significantly increased basal net t-PA antigen release (from -0.8+/-1.0 to 3.2+/-1.2 ng/min/100 mL, P=0.012), but not the release of active t-PA, during either placebo or 17beta-estradiol. Enalaprilat potentiated bradykinin-stimulated vasodilation and t-PA antigen and activity release similarly during placebo and 17beta-estradiol treatment. 17Beta-estradiol treatment does not alter the effect of angiotensin-converting enzyme inhibition on basal t-PA antigen or on bradykinin-stimulated t-PA antigen or activity release. 17Beta-estradiol increases basal release of active t-PA in young postmenopausal women, consistent with enhanced vascular fibrinolytic function.
Lack of direct interaction between enalaprilat and the kinin B1 receptors.
Peptides. 2008 Apr; 29(4): 606-12
Morissette G, Couture JP, Désormeaux A, Adam A, Marceau F
It has been recently proposed that the second extracellular loop of the human bradykinin (BK) B1 receptor (B1R) contains a conserved HExxH motif also present in peptidases possessing a Zn2+ prosthetic group, such as angiotensin converting enzyme (ACE), and that ACE inhibitors directly activate B1R signaling in endothelial cells. However, the binding of ACE inhibitors to the B1Rs has never been directly evaluated. Information about binding of a radiolabeled inhibitor to natural or recombinant ACE in intact cells (physiologic ionic composition) was also collected. We used the tritiated form of an ACE inhibitor previously proposed to activate the B1R, enalaprilat, to address these questions using recombinant human B1Rs and naturally expressed or recombinant ACE. [3H]Lys-des-Arg9-BK bound to the human recombinant B1Rs with high affinity (KD 0.35 nM) in HEK 293a cells. [3H]Enalaprilat (0.25-10 nM) did not bind to cells expressing recombinant human B1R, but bound with a subnanomolar affinity to recombinant ACE or to naturally expressed ACE in human umbilical vein endothelial cells. The radioligand was further validated using a binding competition assay that involved unlabeled ACE inhibitors or their prodrug forms in endothelial cells. Membranes of HEK 293a cells that expressed B1Rs did not hydrolyze hippuryl-glycylglycine (an ACE substrate). Enalaprilat did not stimulate calcium signaling in HEK 293a cells that expressed B1Rs. A typical ACE inhibitor did not bind to nor stimulate the human B1Rs; nevertheless, several other indirect mechanisms could connect ACE inhibition to B1R stimulation in vivo.