rats (SHR) have been reported to differ from those of normotensive Wistar-Kyoto (WKY) rats in response to drugs. The thoracic aorta of SHR gave a smaller relaxant response to acetylcholine (ACh), adenosine (ADO), and isoproterenol (ISO) than did the aorta of WKY.1 " 3 Other investigators found that the ADO-and ISO-induced relaxant responses of the thoracic aorta, perfused mesenteric artery, and perfused hindlimb of SHR were greater than those of WKY.4 " 6 Finally, the contractile response to norepinephrine (NE) of the SHR aorta was either equal to 7 or smaller than 4 8 that of the WKY aorta, but the response of the SHR hindquarters was greater than the WKY counterparts.5 -9 "" The discrepancies remain unexplained but it now appears that the role of the endothelium needs to be considered.In The present work was undertaken to reassess the possible contribution of endothelium to the responses of rat arteries to ACh, ADO, and ISO and, second, to the differences between arteries of SHR and WKY. In addition to the commonly used thoracic aorta and relaxant responses, the femoral artery and NE-induced contraction were studied for comparison purposes. MethodsMale 15-to 16-week-old age-matched SHR and WKY were used. Mean body weights of these rats were 293 ± 5.5 g (n = 17) and 317 ± 4.3 g (n = 20) respectively. Mean systolic blood pressure of SHR and WKY were 186.1 ± 2.3 mm Hg (n = 17) and 135.4 ± 2.0 mm Hg (n = 20) (p < 0.001) by the tail-cuff method in the unanesthetized state. The rat was anesthetized by intraperitoneal pentobarbital (50 rhg/kg) and exsanguinated. The-thorax was opened, and the descending thoracic aorta and femoral artery were immediately excised. After removal of loose connective tissue, a 3 mm-long cylindrical segment was cut from each artery. An adjacent segment was taken after destruction of endothelium; the intimal surface of the aorta was gently rubbed by a wooden rod 1 mm in diameter and that of the femoral artery by a 24-gauge 881 by guest on May 11, 2018 http://hyper.ahajournals.org/ Downloaded from

An arteriovenous vasodilator, flosequinan, has been shown to be effective for the treatment of acute heart failure. However, little is known as to its effect on aortic impedance, which is known to be a proper and precise expression of left ventricular (LV) afterload. To evaluate the acute cardiovascular effect of flosequinan in failing heart, we administered flosequinan intravenously to seven dogs with cardiac failure produced by an infusion of carbon powder (20-50 microm in diameter) into left main trunks of coronary artery. The LV-pump function was severely impaired after intracoronary injection of carbon powder, as evidenced by the findings that cardiac output, circumferential shortening velocity (mean Vcf), and peak +dP/dt of LV pressure were all decreased, associated with a significant increase in LV end-diastolic pressure. Flosequinan (0.9 mg/kg, i.v.) increased cardiac output by 28%, mean Vcf by 44%, and peak +dP/dt by 24%, whereas it decreased total systemic resistance by 32%, time constant of LV pressure decay by 22%, and LV end-diastolic pressure by 18%. Moreover, flosequinan substantially decreased the pulsatile components of LV afterload (i.e., characteristic impedance by 11% and arterial wave reflection coefficient by 45%). Thus flosequinan exerted not only positive inotropic but also positive lusitropic effects, in association with a significant reduction of both pulsatile and steady components of LV afterload, contributing to an improvement of LV-pump function in acute cardiac failure.