Drugs online research references
Lung. 1988;166(4):209-19.
Lung MK 351A uptake after hypoxia adaptation and subsequent hyperoxia exposure.
Jackson RM, Ann HS, Oparil S.
Birmingham Veterans Administration Medical Center, Division of Pulmonary and Critical Care Medicine, AL 35294.
This study investigated the effects of hypoxia adaptation (10% O2 for 4 days) on rat lung angiotensin-converting enzyme (ACE) content before and after hyperoxia exposure (greater than 95% O2 for 2 days). The rationale for this investigation was that hyperoxia exposure decreases lung ACE, while hypoxia adaptation produces tolerance (improved survival) to oxygen toxicity in rats. Rats were exposed to air, hypoxia, hyperoxia alone, or hypoxia followed immediately by hyperoxia. The lungs were then excised and perfused in vitro at 12 ml/min with buffer. Lung ACE content was quantitated by measuring the single-pass binding of an iodinated ACE inhibitor, 125I-MK 351A, a derivative of lisinopril. We showed previously that 125I-MK 351A binding correlates quantitatively with ACE activity in lung homogenates and isolated, perfused lungs. Lung internal surface area was estimated by measuring the mean alveolar diameter of 5 micron hematoxylin and eosin sections from lungs fixed in inflation (25 cmH2O transpulmonary pressure). Hypoxia adaptation per se had no effect on 125I-MK 351A binding or estimated alveolar surface area, while hyperoxia exposure caused a significant decrease in both 125I-MK 351A binding and alveolar surface area. These hyperoxia-induced decreases were prevented partially by hypoxia adaptation, indicating a protective effect on both ACE content and surface area. 125I-MK 351A binding in isolated perfused lungs changed in parallel with histologically estimated surface area. These results indicate that hypoxia preadaptation minimizes the oxygen-induced decrease in lung microvascular ACE content.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2849698&dopt=Abstract
Clin Cardiol. 1991 Jul;14(7):579-82.
Acute effects of the ACE inhibitor lisinopril on cardiac electrophysiological parameters of isolated guinea pig hearts.
Stark G, Stark U, Nagl S, Klein W, Pilger E, Tritthart HA.
Department of Internal Medicine, Karl Franzens University, Graz, Austria.
Angiotensin-converting enzyme (ACE) inhibitors are of benefit in life-threatening ventricular arrhythmias in patients with congestive heart failure and ventricular tachycardia caused by the onset of myocardial ischemia as well as by reperfusion of an ischemic area. The aim of the present study was to investigate whether direct electrophysiological effects are responsible for these observations. Therefore, we investigated the electrophysiological effects of lisinopril on the whole cardiac conduction and pacemaker system in isolated guinea pig hearts perfused by the method of Langendorff at concentrations of 0.01, 0.1, 1, and 10 microM. Lisinopril did not affect heart rate, atrioventricular, His bundle, or intraventricular conduction at any of the concentrations tested. Likewise the frequency-dependent QT duration was unchanged. At a concentration of 10 microM, lisinopril prolonged effective refractory period evaluated by premature beats (46 +/- 15%, n = 8, p less than 0.01) as well as the rate-dependent effective refractory period (31 +/- 12, n = 8, p less than 0.01) of the atrioventricular conduction. These effects can be explained by lisinopril's action as a minor calcium antagonist at a toxic concentration of 10 microM. The present results show that electrophysiological parameters are not substantially altered by lisinopril. Therefore, several other mechanisms such as the unloading of the left ventricle and/or the suppression of noradrenalin release and the electrolyte (potassium and magnesium) repletion and/or regression of left ventricular hypertrophy as long-term effects may play a major role in the antiarrhythmic efficacy of ACE inhibitors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1660796&dopt=Abstract
Eur J Pharmacol. 1994 Feb 15;266(3):201-11.
Structural constraints of inhibitors for binding at two active sites on somatic angiotensin converting enzyme.
Perich RB, Jackson B, Johnston CI.
University of Melbourne, Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Angiotensin converting enzyme active sites from rat plasma, lung, kidney and testis were assessed by comparative radioligand binding studies under physiological chloride conditions. Displacement of [125I]Ro 31-8472 from somatic and plasma angiotensin converting enzyme by angiotensin converting enzyme inhibitors of different structure indicated two binding sites (perindoprilat: high affinity carboxyl site, KDC 18 +/- 6 pM), and a single high affinity binding site on testis angiotensin converting enzyme (KDC 20 +/- 1 pM). Displacement of [125I]351A from plasma, somatic and testis angiotensin converting enzyme occurred at a single high affinity binding site. Reduction in affinity at the amino binding site of somatic angiotensin converting enzyme was related to an increased side chain size (lung KDA (pM): Ro 31-8472 175 +/- 38, lisinopril 2205 +/- 1832, and 351A 2271 +/- 489), or hydrophobicity of the competing unlabelled angiotensin converting enzyme inhibitor (lung KDA (pM): quinaprilat 1267 +/- 629 and perindoprilat 824 +/- 6). This trend was reversed at the carboxyl binding site of plasma, somatic and testis angiotensin converting enzyme. Bradykinin hydrolysis by lung angiotensin converting enzyme was inhibited in a similar manner by cilazaprilat or quinaprilat (F = 0.64, F-test based on the extra sum-of-squares principle; P > 0.05), indicating the angiotensin converting enzyme carboxyl active site predominates in bradykinin cleavage. The data demonstrate that the two binding sites on native plasma and somatic angiotensin converting enzyme are of potentially different functional and structural nature, suggesting they may have different substrate specificities.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8174603&dopt=Abstract
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Amoxicillin ||
Tramadol ||
Paxil ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Zithromax ||
online pharmacy ||
Antibiotics and prescription medications online literature ||
Antibiotics