Objectives: We previously showed that an angiotensin-converting enzyme inhibitor (captopril) or an angiotensin receptor blocker (losartan) reduced infarct size and improved endothelial function in a rat model of ischaemia-reperfusion. The present study was undertaken to see if aspirin (ASA) antagonised the beneficial effects of captopril or losartan.
Methods: One hundred and fourteen Sprague-Dawley rats were randomised into six groups; Control, ASA, captopril, losartan, ASA+captopril, and ASA+losartan. ASA, captopril or losartan were given at a concentration of 40 mg/kg/day in drinking water. After six weeks of pre-treatment, the rats were subjected to 17 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion, with haemodynamic and ECG monitoring. During the reperfusion period, the effective refractory period (ERP), ventricular fibrillation threshold (VFT) and bleeding time (BT) were measured. In fresh aortic rings precontracted with phenylephrine, endothelium-dependent and -independent relaxations were assessed using acetylcholine and nitroglycerin.
Results: Haemodynamic changes were not different between the groups. Serum ASA concentrations were 0.5, 1.1 and 0.6 mg/dl in the ASA, ASA+captopril and ASA+losartan groups, respectively, and BT was prolonged (p<0.01). ASA alone reduced endothelium-dependent relaxation (-29+8 vs. -69+11%, p<0.01), but did not change endothelium-independent relaxation. ASA did not affect endothelial relaxation induced by acetylcholine in the presence of either captopril or losartan. Angiotensin I and ERP were elevated by captopril and losartan. Angiotensin II and VFT were elevated by losartan. ASA with captopril, captopril and losartan equally reduced infarct size, compared with control (39+3, 39+4, and 39+5 vs. 53+3%, all p<0.05).
Conclusions: Captopril and losartan had similar cardiovascular protective effects in a rat model of ischaemia-reperfusion. Aspirin did not attenuate the cardiovascular protective effects of captopril or losartan.
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http://dx.doi.org/10.3317/jraas.2003.005 | DOI Listing |
J Cardiothorac Vasc Anesth
January 2025
Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA.
Vasoplegia is a pathophysiologic state of hypotension in the setting of normal or high cardiac output and low systemic vascular resistance despite euvolemia and high-dose vasoconstrictors. Vasoplegia in heart, lung, or liver transplantation is of particular interest because it is common (approximately 29%, 28%, and 11%, respectively), is associated with adverse outcomes, and because the agents used to treat vasoplegia can affect immunosuppressive and other drug metabolism. This narrative review discusses the pathophysiology, risk factors, and treatment of vasoplegia in patients undergoing heart, lung, and liver transplantation.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Division of Pharmacology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan.
The pathogenesis of painful diabetic neuropathy (PDN) is complicated and remains not fully understood. A disintegrin and metalloprotease 17 (ADAM17) is an enzyme that is responsible for the degradation of membrane proteins. ADAM17 is known to be activated under diabetes, but its involvement in PDN is ill defined.
View Article and Find Full Text PDFClin Sci (Lond)
January 2025
Center for Interdisciplinary Research in Biology, College de France, Institut National de la Santé et de la Recherche Médicale, Paris, France.
Apelin, a (neuro) vasoactive peptide, plays a prominent role in controlling water balance and cardiovascular functions. Apelin and its receptor co-localize with vasopressin in magnocellular vasopressinergic neurons. Apelin receptors (Apelin-Rs) are also expressed in the collecting ducts of the kidney, where vasopressin type 2 receptors are also present.
View Article and Find Full Text PDFDiabetol Int
January 2025
First Department of Medicine, Wakayama Medical University, 811‑1 Kimi‑idera, Wakayama, 641‑8509 Japan.
Sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNI), is becoming more common in the treatment of heart failure and hypertension. Neprilysin is highly expressed in the renal tubules, and reports have shown increases in urinary C-peptide reactivity (CPR) levels after administration of ARNI. However, the effect of ARNI on serum CPR levels, a critical marker of insulin secretion in diabetes, remains underexplored.
View Article and Find Full Text PDFObjectives: This clinical study assessed the three-year, long-term effects of esaxerenone, a non-steroidal aldosterone receptor blocker, on Japanese patients with type 2 diabetes, diabetic kidney disease, and hypertension who were receiving renin-angiotensin system inhibitors.
Materials And Methods: Data from a computerized diabetic care database were used to retrospectively compare esaxerenone users (Group A) with non-esaxerenone users (Group B). Propensity score weighting was applied to Group B.
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