臺灣博碩士論文加值系統

本篇論文在探討quinazoline衍生物DL-017在麻醉的Sprague-Dawley大白鼠及自發性高血 壓大白鼠上的降血壓機轉研究。研究方法採股動靜脈插管，並且經靜脈給藥以測量血壓及心率之變化。其結果顯示DL-017或prazosin皆可導致全身血壓及心率的下降 (部分樣本於最初時會出現短暫的心跳增快)。兩者在0.1 mg/kg的劑量下即可產生最大的降血壓作用。單一劑量phenylephrine (PHE) (3 *g/kg)或血管張力素II (angiotensin II, AII；0.1 *g/kg)會引發短暫的全身血壓上升及反射性心跳減緩； Nω-nitro-L-arginine (L-NNA，一種強效的一氧化氮合成酵素抑制劑) (30 mg/kg)造成持久性的全身血壓上升及心跳減緩。其中PHE所引發的升血壓作用會被DL-017及prazosin所拮抗，但AII及L-NNA所引發者則否。相對於prazosin而言，DL-017呈現了明顯增強AII引發血壓上升後的反射性心跳減緩現象。此些結果暗示了DL-017相似於prazosin皆可經由拮抗*1的作用而導致血壓的下降，並且也功能性地減弱了因AII接受器興奮或一氧化氮合成酵素受抑制所引發的升血壓作用。

Mechanisms of hypotensive effects of 3-（（4-(2-methoxy-phenyl)piperazin-l-ly）methylthio）-2, 3-dihydroimidazo （1, 2-c）quinazoline (DL-017), a synthesized quinazoline derivative, were studied in anaesthetized Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR).Intravenous administration of DL-017 or prazosin resulted in falls in systemic arterial blood pressure (SAP) and, except initial transient increase in some preparations, heart rate (HR) in both SD and SHR.At a dose of 0.1 mg/kg, DL-017 exerted a maximal hypotensive effect. Phenylephrine (PHE) (3*g/kg) or angiotensinⅡ (AⅡ) (0.1 *g/kg) induced a transient increase in SAP with a reflex bradycardia, while Nω-nitro-L-arginine (L-NNA, a potent nitric oxide synthase inhibitor) (30 mg/kg)produced a long-lasting increase in SAP and decrease in HR. DL-017 as well as prazosin selectively antagonized the pressor effect of PHE, but not that of AⅡ or L-NNA. In comparison with prazosin, DL-017 enhanced reflex bradycardia in response to pressor effect of AⅡ. These results suggest that DL-017, similar to prazosin, exerts an α1-antagonistic action to lower blood pressure and functionally attenuates the hypertensive effect from stimulation of AⅡ receptor and inhibition of nitric oxide synthase.