Orthosiphon stamineus Benth has been traditionally used to treat hypertension. The study aimed to investigate the vascular reactivity of water extract (WOS) and water？:？methanolic (1？:？1) extract (WMOS) of Orthosiphon stamineus Benth and AT1 receptors blocker in the mechanisms of antihypertensive mediated by α1-adrenergic receptor and EDNO and PGI2 releases in the SHR aortic rings. SHR (230–280？g) were divided into four groups: control, WOS, WMOS, and losartan. After being fed orally for 14 days, the aorta was harvested and subjected to PE (10？9 to 10？5？M) and ACh (10？9 to 10？5？M) with and without L-NAME (100？μM) and indomethacin (10？μM), respectively. WOS, WMOS, and losartan significantly reduced the contractile responses to PE intact suggesting the importance of endothelium in vasorelaxation. Losartan significantly enhanced the ACh-induced vasorelaxation. L-NAME significantly inhibited the ACh-induced relaxation in all groups. Indomethacin enhanced ACh-induced vasorelaxation in WMOS. Collectively, Orthosiphon stamineus leaves extract reduced vasoconstriction responses by the alteration of α1-adrenergic and AT1 receptors activities. The involvement of EDNO releases was clearly observed in this plant. In WOS, PGI2 releases might not participate in the ACh-induced vasorelaxation. However, in WMOS, enhancement of vasorelaxation possibly due to continuous release of PGI2. 1. Introduction Orthosiphon stamineus Benth (syn.: O. aristatus (Bl.) Miq., O. grandiflorus Bold., O. spicatus (Thumb) Bak.; Lamiaceae) [1], or locally known as “Misai Kucing,” leaves extracts have been used as traditional medicine [2] and possess benefits such as antidiabetic, ability to increase plasma triglyceride and plasma HDL-cholesterol concentrations [3], anti-lithiatic and hypouricemic effects [4, 5], antifungal [6], and ability to treat kidney stone and urinary tract diseases [7–9]. It has traditionally been used in Java for the treatment of hypertension and diabetes [1]. Hypertension has been reported to be associated with endothelium dysfunction in both human and animal studies [10]. Endothelium regulates vascular tone by releasing vasoconstrictors such as endothelins, prostanoids and oxygen reactive species, and vasodilators such as nitric oxide (NO), prostacyclin (PGI2), and endothelial hyperpolarizing factor (EDHF). These vasodilators were a great discovery by Furchgott and Zawadzki in 1980 [11], known as endothelium derived relaxing factors (EDRF). It has been reported by Peach et al. [12] that releases of EDRF caused vasorelaxant effects of acetylcholine (ACh), which is
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