Avtor/Urednik     Lunder, Mojca; Janić, Miodrag; Žiberna, Lovro; Drevenšek, Gorazd; Šabovič, Mišo
Naslov     A low-dose atorvastatin and losartan combination directly improves aortic ring relaxation and diminishes ischaemic-reperfusion injury in isolated rat hearts
Tip     članek
Vir     Med Sci Monit
Vol. in št.     Letnik 18, št. 9
Leto izdaje     2012
Obseg     str. BR366-374
ISSN     1234-1010
Jezik     eng
Abstrakt     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 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 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 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.<br />
Deskriptorji     HEART
ANTILIPEMIC AGENTS
RECEPTORS, ANGIOTENSIN
MYOCARDIAL REPERFUSION INJURY
AORTA, THORACIC
ENDOTHELIUM, VASCULAR
VASODILATION
NITRIC-OXIDE SYNTHASE
RATS, WISTAR