Influenza virus can infect vascular endothelium and cause endothelial dysfunction. Persons at higher risk for severe influenza are patients with acute and chronic cardiovascular disorders; however, the mechanism of influenza-induced cardiovascular system alteration remains not fully understood. Thirty Wistar rats were divided in six groups – four experimental and two control. Rats from each experimental group were treated with doxorubicin following echocardiography confirmation of acute cardiotoxicity. Two groups of rats were intranasally inoculated with rat-adapted influenza A(H1N1)pdm09 virus, while two other groups – with α-MEM. After 24 and 96 hours mesenteric vessels were harvested for studying vasomotor activity using wire myograph and endothelial factors (eNOS, PAI-1 and tPA) expression by immunohistochemistry; PAI-1 and tPA concentration was analyzed in blood plasma by ELISA. Significant decrease in maximal response of mesenteric arteries of infected rats with premorbid acute cardiomyopathy to both vasoconstrictor and vasodilator at 24 and 96 hpi was registered compared to uninfected rats with acute cardiomyopathy and control rats. Expression of eNOS in mesenteric vascular endothelium was modulated at 24 and 96 hpi. PAI-1 expression was increased by 3.47-fold at 96 hpi, while concentration of PAI-1 in the blood plasma was increased by 6.43-fold at 24 hpi compared with uninfected rats with acute cardiomyopathy. tPA concentration in plasma was also modulated at 24 hpi and 96 hpi compared with uninfected rats with acute cardiomyopathy. The obtained data indicate that influenza A(H1N1)pdm09 virus in rats aggravates the course of premorbid acute cardiomyopathy causing a pronounced dysregulation of endothelial factors expression and vasomotor activity impairment of mesenteric arteries.