Angiotensin converting enzyme inhibitor captopril does not improve exercise tolerance or reduce exercise induced myocardial ischemia in patients with angina pectoris (original) (raw)
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Canadian Journal of Physiology and Pharmacology, 2004
Retrospective examination of acute gastrointestinal (GI) lethality in our rat bone marrow transplantation studies showed indication of a protective effect, with a dose modifying factor (DMF) of 1.06 (95% confidence interval: 0.99-1.12). A randomized study, using the same experimental design, was conducted specifically to look for GI protection. Animals were randomized into captopril or non-drug arms and irradiated in a 6-fraction total body irradiation regimen, followed by bone marrow transplantation. Rats received captopril in the drinking water at 500 mg/l (70 mg/kg/day), starting 9 days prior to irradiation and continuing throughout the experiment. The 50% lethal dose at 6 days was 20.8 (20.4-21.7) Gy in the non-drug arm and 20.6 (20.3-20.9) Gy in the captopril arm, for a DMF of 0.99 (0.94-1.04). If the randomized and historical studies are combined the DMF is 1.00 (0.93-1.05). We are unable to find any evidence that the angiotensin converting enzyme (ACE) inhibitor captopril provides protection from acute GI injury in this model. Clearly, it should not be assumed that captopril will modulate radiation reactions in all tissues.
Effect of captopril on changes in rats' hearts induced by long-term irradiation
Radiation …, 1993
The aim of this study was to test the efficacy of captopril, an angiotensin-converting enzyme inhibitor and a known suppressor of fibrosis, in preventing late radiation-induced cardiac pathology. Myocardial functional, histochemical and ultrastructural-morphometric studies were done on perfused hearts of rats isolated 3 and 6 months after 60Co Y irradiation with 20 Gy and age-matched controls. At each time the animals were divided into the following groups: nonirradiated controls; irradiated once with 20 Gy; irradiated as above and given daily doses of captopril; daily doses of captopril without irradiation. The results showed that captopril, while ameliorating the decrease in the indices of capillary function, increase in mast cells, fibrosis, number of atrial granules, and changes in nerve terminals, failed to prevent the progressive functional deterioration of the hearts after irradiation. These findings suggest that an intramyofiber derangement may be involved in the long-term myocardial complications of irradiation.
Effect of Time and Dose on Angiotensin Converting Enzyme during Captopril Treatment in the Rat
Acta Pharmacologica et Toxicologica, 1983
The effect of treatment time and dose of captopril with regard to angiotensin converting enzyme (ACE) in serum, lungs and kidneys of the rat were studied. Normotensive Wistar rats were treated with a constant dose of captopril (0.2 mg/ml) during various time periods. In a second study rats were treated with different captopril doses (6.25 pg, 12.5 pg, 25 pg, 50 pg, and 200 pg/ml water) during three weeks. Serum ACE activity and pulmonary and kidney plasma membrane ACE concentrations were measured in both studies. Captopril treatment resulted in a rapid decrease of ACE in pulmonary and kidney plasma membranes and a simultaneously increase of serum ACE activity during the first day of treatment. This was followed by increased membrane concentrations of ACE in the lungs and return to normal ACE concentrations in membranes of kidneys, presumably due to increased ACE biosynthesis. Serum ACE activity continued to increase during the whole study. Serum ACE activity increased in a dose dependent manner during treatment with different captopril doses. Increased plasma membrane ACE concentrations were not observed in the rats treated with captopril at doses below 200 pg/ml water.
Acta Pharmacologica et Toxicologica, 1983
Serum ACE activity increased as expected about three-fold following six weeks of captopril (30 mg/kg/day) treatment in Wistar rats (n=9). The effect on serum and lung ACE activity and concentration, respectively, was studied after captopril discontinuation. Serum ACE activity was measured at start and 3, 6 , and 12 days after captopril withdrawal. The approximal half-life of serum ACE activity was 72 hours as judged from the decrease rate after stimulated ACE biosynthesis induced by captopril. No differences in lung plasma membranes and lung homogenate ACE concentrations between treated and untreated rats were observed 12 days after discontinuation of captopril treatment. Serum ACE activity remained unchanged in the control rats (n=9). We conclude that induction of ACE biosynthesis in the rat is reversible after withdrawal of captopril.
Mitigation of radiation induced pulmonary vascular injury by delayed treatment with captopril
Respirology, 2012
Background and objective: A single dose of 10 Gy radiation to the thorax of rats results in decreased total lung angiotensin-converting enzyme (ACE) activity, pulmonary artery distensibility and distal vascular density while increasing pulmonary vascular resistance (PVR) at 2-months post-exposure. In this study we evaluate the potential of a renin-angiotensin system (RAS) modulator, the ACE inhibitor captopril, to mitigate this pulmonary vascular damage. Methods: Rats exposed to 10 Gy thorax only irradiation and age-matched controls were studied 2-months after exposure, during the development of radiation pneumonitis. Rats were treated, either immediately or 2-weeks after radiation exposure, with 2 doses of the ACE inhibitor, captopril, dissolved in their drinking water. To determine pulmonary vascular responses, we measured pulmonary hemodynamics, lung ACE activity, pulmonary arterial distensibility, and peripheral vessel density. Results: Captopril, given at a vasoactive but not a lower dose, mitigated radiation-induced pulmonary vascular injury. More importantly these beneficial effects were observed even if drug therapy was delayed for up to two weeks after exposure. Conclusions: Captopril resulted in a reduction in pulmonary vascular injury that supports its use as a radiomitigator after an unexpected radiological event such as a nuclear accident.
Experimental biology and medicine (Maywood, N.J.), 2001
Nephropathy, interstitial pneumopathy, and renal and lung fibrosis are major complications of bone marrow transplantation (BMT). This study evaluated the antifibrotic property of an angiotensin II (A2) type-1 receptor blocker (L-159,809) and compared it with those of Captopril and Enalapril, two angiotensin-converting enzyme (ACE) inhibitors, in a rat model of BMT. Male WAG/Rij/MCW rats received a preparative regimen of 60 mg/kg body wt of cytoxan (i.p., Days 9 and 8) and 18.5 Gy of total body irradiation (TBI) in six twice daily fractions (Days 2, 1, and 0) followed immediately (Day 0) by BMT. Modifiers were given in drinking water from Day 10 until autopsy, 8 weeks after BMT. Rats treated with TBI plus cytoxan alone developed severe nephropathy. Trichrome staining showed marked collagen deposition in glomeruli, renal interstitium, and renal arteries and arterioles (especially in their adventitia). Collagen deposition and renal damage were markedly reduced by the three modifiers. O...
Up-regulation of angiotensin-converting enzyme and angiotensin II type 1 receptor in irradiated rats
International Journal of Radiation Biology, 2010
We investigated in Lewis normotensive rats the effect of coronary artery ligation on the expression of cardiac angiotensin-converting enzymes (ACE and ACE 2) and angiotensin II type-1 receptors (AT 1a -R) 28 days after myocardial infarction. Losartan, olmesartan, or the vehicle (isotonic saline) was administered via osmotic minipumps for 28 days after coronary artery ligation or sham operation. Coronary artery ligation caused left ventricular dysfunction and cardiac hypertrophy. These changes were associated with increased plasma concentrations of angiotensin I, angiotensin II, angiotensin-(1-7), and serum aldosterone, and reduced AT 1a -R mRNA. Cardiac ACE and ACE 2 mRNAs did not change. Both angiotensin II antagonists attenuated cardiac hypertrophy; olmesartan improved ventricular contractility. Blockade of the AT 1a -R was accompanied by a further increase in plasma concentrations of the angiotensins and reduced serum aldosterone levels. Both losartan and olmesartan completely reversed the reduction in cardiac AT 1a -R mRNA observed after coronary artery ligation while augmenting ACE 2 mRNA by approximately 3-fold. Coadministration of PD123319 did not abate the increase in ACE 2 mRNA induced by losartan. ACE 2 mRNA correlated significantly with angiotensin II, angiotensin-(1-7), and angiotensin I levels. These results provide evidence for an effect of angiotensin II blockade on cardiac ACE 2 mRNA that may be due to direct blockade of AT 1a receptors or a modulatory effect of increased angiotensin-(1-7). (Hypertension. 2004;43:970-976.)