Author/Editor		Janić, Miodrag; Lunder, Mojca; Černe, Darko; Marc, Janja; Jerin, Aleš; Skitek, Milan; Drevenšek, Gorazd; Šabovič, Mišo
Title		The rise-peak-fall pattern of time-dependency of the cardiovascular pleiotropic effects of treatment with low-dose atorvastatin, losartan and a combination thereof in rats
Type		članek
Vol. and No.		Letnik 68, št. 1
Publication year		2016
Volume		str. 74-80
ISSN		0160-2446 - Journal of cardiovascular pharmacology
Language		eng
Abstract		Treatment with low, sub-therapeutic doses of statins and sartans expresses beneficial pleiotropic effects on the arterial wall. The present study explored whether these effects depend on treatment duration. Wistar rats were randomly divided into four groups and daily received low-dose atorvastatin, low-dose losartan, their combination or saline (control). After 4, 6, 8 and 10 weeks of treatment, the animals were anesthetized, blood samples taken and hearts and thoracic aortas isolated. Thoracic aorta endothelium-dependent relaxation and parameters of the isolated heart exposed to ischemic-reperfusion injury were assessed along with blood serum parameters and vasoactive genes expression. Low-dose atorvastatin, losartan and especially their combination showed the characteristic time-dependency of all studied parameters (thoracic aorta relaxation, isolated heart parameters, C-reactive protein values, genes encoding endothelial nitric oxide synthase and CD 40). The peak in efficacy was observed after 6 weeks of treatment, and subsequently steadily declined. The peak versus control values were significant for all measured parameters. Only a combination of atorvastatin and losartan increased nitric oxide and decreased asymmetric dimethylarginine (ADMA). A characteristic time-dependent rise-peak-fall pattern of the cardiovascular pleiotropic effects of statins and sartans in sub-therapeutic low-doses was revealed. Evidently, resistance to the explored treatment occurs after a certain period.