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Potential adverse interaction between aspirin and lisinopril in hypertensive rats
K Dubey1, D K Balani, K K Pillai
1Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110 062, India. kdb104@rediffmail.com
Insights
Aspirin (ASA) combined with ACE inhibitors did not affect blood pressure reduction in rats. However, higher doses of ASA increased mortality and caused organ damage, suggesting it may reduce survival benefits.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Toxicology
Background:
- The concurrent use of aspirin (ASA) and angiotensin-converting enzyme (ACE) inhibitors presents a clinical dilemma.
- Previous research suggests ASA may diminish the therapeutic benefits of ACE inhibitors in conditions like hypertension, heart failure, and coronary artery disease.
- Concerns exist regarding the safety of combining ASA with ACE inhibitors.
Purpose of the Study:
- To investigate the interaction between aspirin (ASA) and ACE inhibitors in a rat model of hypertension.
- To evaluate the impact of concurrent ASA administration on the efficacy and safety of Lisinopril (LS) in hypertensive rats.
Main Methods:
- Hypertension was induced in male Wistar rats using Methylprednisolone (MP).
- Rats were treated with Lisinopril (LS) alone or in combination with two different doses of ASA (100 mg/kg and 25 mg/kg).
- Systolic blood pressure (SBP) was monitored noninvasively, and histopathological examination assessed cardiac and renal tissues.
Main Results:
- Concurrent ASA treatment did not impede the blood pressure-lowering effects of LS at either dose.
- High-dose ASA (100 mg/kg) led to significant mortality, cardiac necrosis, and renal damage.
- Lower-dose ASA (25 mg/kg) resulted in reduced mortality but showed variable effects on cardiac and renal tissues.
- ASA attenuated the survival benefits of ACE inhibitors in hypertensive rats, with a more pronounced effect at the higher dose.
Conclusions:
- Aspirin (ASA) does not interfere with the antihypertensive efficacy of ACE inhibitors (Lisinopril) in this rat model.
- High-dose ASA poses significant risks, including increased mortality and severe organ damage (cardiac and renal).
- Aspirin may counteract the survival advantages conferred by ACE inhibitors in hypertensive conditions, particularly at higher dosages.
Abstract:
The potential clinical effect of aspirin (ASA) in patients treated with angiotensin converting enzyme (ACE) inhibitors is debatable. Several studies have suggested that ASA attenuates the beneficial effects of ACE inhibitors in hypertension, congestive heart failure (CHF) or coronary artery disease (CAD) and have questioned the safety of using ASA concomitantly with these agents. The present study aims to investigate the possible interaction between ASA and ACE inhibitor in hypertensive rats. Hypertension was induced in adult male Wistar rats using Methylprednisolone (MP) 20 mg/kg per week s.c. for 2 weeks. The systolic blood pressure (SBP) was measured by noninvasive BP technique. The effect of Lisinopril (LS) 15 mg/kg per day and that of combination of LS and ASA; 100 and 25 mg/kg per day p.o. was studied on hypertension induced by glucocorticoid. Concurrent ASA treatment with LS did not hinder the hypotensive effect of LS at either dose. However ASA 100 mg/kg per day caused mortality in animals and produced massive cardiac necrosis and renal damage as evident from histopathology. Treatment with ASA 25 mg/kg per day caused lower mortality with variable effects on cardiac and renal tissues. These results indicate that ASA attenuates the beneficial effects of ACE inhibitor on survival in hypertensive rats and this effect was more pronounced at higher dose of ASA.