. Cedrelopsis grevei induced hypotension and improved endothelial vasodilatation through an increase of Cu/Zn SOD protein expression. Am J Physiol Heart Circ Physiol 286: H775-H781, 2004. First published November 6, 2003 10.1152/ajpheart.00584.2003.-This study was designed to investigate the cardiovascular consequences of oral administration of Cedrelopsis grevei (CG) in normotensive rats. Experiments were designed to investigate hemodynamic parameters in vivo as well as the consequences of CG treatment on the vasoconstriction response to norepinephrine and the vasorelaxant response to ACh ex vivo in isolated aortas and small mesenteric arteries (SMA). Treatment of male Wistar rats with 80 mg/kg CG for 4 wk induced a progressive decrease in systolic blood pressure. In the aorta, CG did not significantly alter the response to norepinephrine despite the participation of extraendothelial nitric oxide (NO)-induced hyporeactivity. In the SMA, contraction to norepinephrine was not modified by CG treatment even though it enhanced the participation of endothelial NO. Endothelium-dependent relaxation to ACh was increased in both the aorta and SMA from CG-treated rats. In the aorta from CG-treated rats, the mechanism involved superoxide dismutase (SOD)-and catalase-sensitive free radical production. The latter was associated with enhanced expression of Cu/Zn SOD and endothelial NO synthase. These results suggest that oral administration of CG produces a decrease in blood pressure in normotensive rats. This hemodynamic effect was associated with enhanced endothelium-dependent relaxation and an induction of Cu/Zn SOD and endothelial NO synthase expressions in the vessel wall. They also show subtle mechanisms that compensate for the increased participation of NO to maintain unchanged agonistinduced contractility. These data provide a pharmacological basis for the empirical use of CG against cardiovascular diseases. blood pressure; vasoconstriction CEDRELOPSIS GREVEI (CG) Baill (Meliaceae) is an endemic plant from the southern and western areas of Madagascar empirically used against pulmonary diseases such as cough, tuberculosis, and pneumonia. This plant is also used as an antiasthenic, anti-inflammatory, and antihypertensive drug (4, 5, 10).Different classes of compounds have been isolated from CG including chromones, coumarins, triterpenoids, limonoids, and polyphenols (9,13,20,27). These compounds are known to be biologically active and beneficial against different pathologies such as inflammation, cancer, and cardiovascular diseases (15,19). Among these compounds, the most active are the molecules from the class of polyphenols and coumarins. Indeed, they have been reported to scavenge reactive oxygen species (ROS), inhibit oxidation of low-density lipoprotein, prevent platelet aggregation, induce vasorelaxation, and interact with the nitric oxide (NO) pathway (1,2,14,16,22,23).Very recently, we reported that a crude extract of CG was able to induce relaxation of the rat aorta in both the presence or absence of functiona...