Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

30 August 2012

A low-dose atorvastatin and losartan combination directly improves aortic ring relaxation and diminishes ischaemic-reperfusion injury in isolated rat hearts

Mojca LunderABCDEF, Miodrag JanićCDEF, Lovro ŽibernaBCDEF, Gorazd DrevenšekADEG, Mišo ŠabovičADEFG

DOI: 10.12659/MSM.883347

Med Sci Monit 2012; 18(9): BR366-374

Abstract

Background: The cardiovascular pleiotropic effects of statins and angiotensin receptor blockers (ARBs) could be of interest for innovative preventive approaches. We aimed to investigate whether low-dose atorvastatin and losartan, separately not possessing protective cardiovascular pleiotropic effects, express them when combined.
Material/Methods: Forty-five adult male Wistar rats were anaesthetized and their thoracic aortas and hearts were isolated. Relaxation of aortic rings, coronary flow rate and the extent of myocardial ischaemic-reperfusion injury were measured. Different concentrations (0.01, 0.1, 1.0 µM) of atorvastatin and losartan added to a perfusion medium were first tested. The separate drugs, which were ineffective, were then combined at the same concentrations and the concentration was tested in the same model.
Results: Low concentrations of atorvastatin or losartan (0.1 and 1 µM, respectively) produced no effects in isolated aorta. However, surprisingly, when these drug concentrations were combined, a significantly improved endothelium-dependent relaxation of the thoracic aorta was observed. Similarly, when combining individually ineffective concentrations of atorvastatin or losartan (0.01 and 0.1 µM, respectively), significantly increased coronary flow and a decreased extent of myocardial injury were observed. By using a nitric oxide-synthase inhibitor, we demonstrated that the vasodilatory effects obtained were nitric oxide-dependent. The degree of effectiveness by the combination was comparable to that obtained by 10-fold (atorvastatin) or 100-fold (losartan) higher concentrations of the separate drugs.
Conclusions: Our results revealed that remarkable additive/synergistic effects exist between low-doses of a statin (atorvastatin) and an ARB (losartan), resulting in important cardiovascular protection. This new concept could be valuable in cardiovascular prevention.

Keywords: Regional Blood Flow - drug effects, Rats, Wistar, Pyrroles - therapeutic use, Muscle Relaxation - drug effects, Losartan - therapeutic use, Heptanoic Acids - therapeutic use, Drug Therapy, Combination, Dose-Response Relationship, Drug, Coronary Vessels - physiology, Aorta - drug effects, Analysis of Variance, Reperfusion Injury - prevention & control

Add Comment 0 Comments

1153 2

Editorial

01 December 2023 : Editorial  

Editorial: Outbreaks of Post-Pandemic Childhood Pneumonia and the Re-Emergence of Endemic Respiratory Infections

Dinah V. Parums

DOI: 10.12659/MSM.943312

Med Sci Monit 2023; 29:e943312

0:00

In Press

01 Dec 2023 : Clinical Research  

Risk Factors and Clinical Outcomes of COVID-19 Infection in Multiple Sclerosis Patients: A Retrospective St...

Med Sci Monit In Press; DOI:  

30 Nov 2023 : Review article  

Decoding the Neurological Sequelae of General Anesthesia: A Review

Med Sci Monit In Press; DOI:  

30 Nov 2023 : Clinical Research  

Enhanced Pain Relief and Muscle Growth in Individuals with Low Back Instability: The Impact of Blood Flow R...

Med Sci Monit In Press; DOI:  

29 Nov 2023 : Clinical Research  

Comparative Analysis of Intramedullary Nail versus Plate Fixation for Fibula Fracture in Supination Externa...

Med Sci Monit In Press; DOI:  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

0:00

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750