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A low-dose atorvastatin and losartan combination directly improves aortic ring relaxation and diminishes ischaemic-reperfusion injury in isolated rat heartsLunder, Mojca, dr. med. ...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.<br /> Material/Methods: Forty-five adultmale 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 microM) 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.<br /> Results: Low concentrations of atorvastatin or losartan (0.1 and 1 microM, 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 microM, 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.<br /> Conclusions: Our results revealed that remarkable additive/synergistic effectsexist between low-doses of a statin (atorvastatin) and an ARB (losartan), resulting in important cardiovascular protection. This new conceptcould be valuable in cardiovascular prevention.<br />Vir: Medical Science Monitor. - ISSN 1234-1010 (Vol. 18, iss. 9, 2012, str. BR366-BR374)Vrsta gradiva - članek, sestavni delLeto - 2012Jezik - angleškiCOBISS.SI-ID - 30127577
Avtor
Lunder, Mojca, dr. med. |
Janić, Miodrag |
Žiberna, Lovro |
Drevenšek, Gorazd |
Šabovič, Mišo
Teme
Heart |
Drug Effects |
Antilipemic Agents |
Receptors, Angiotensin |
Antagonists And Inhibitors |
Myocardial Reperfusion Injury |
Aorta, Thoracic |
Drug Effects |
Endothelium, Vascular |
Vasodilation |
Nitric-Oxide Synthase |
Rats, Wistar |
Lipolitiki |
Srce |
Receptorji, angiotenzin |
Miokardna, reperfuzijska poškodba |
Aorta torakalna |
Podgane, Wistar |
Endotelij žilni |
Dušikov-oksid, sintaza |
Vazodilatacija
Vnos na polico
Trajna povezava
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| Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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| Lunder, Mojca, dr. med. | 28865 |
| Janić, Miodrag | 33911 |
| Žiberna, Lovro | 29416 |
| Drevenšek, Gorazd | 13310 |
| Šabovič, Mišo | 08094 |
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