The Mechanism Of Depressor Effect Of Rutaecarpine In The Two-kidney-one-clip Hypertensive Rats.

Aim: To explore the antihypertensive effect of rutaecarpine(Rut) in two-kidney- one-clip hypertensive rats and elucidate whether or not the mechanism of antihypertensive effect of Rut is related to enhanced expression of CGRP and the activation of prolylcarboxypeptidase (PRCP), which can inactivate angiotensinâ…¡and activate prekallikrein.Methods: Two-kidney-one-clip(2K1C) hypertensive rat model was used in the experiment; blood pressure (BP) was measured by tail-cuff method. The mesentery arteries and thoracic arteries were sheared and preserved in 10% formalin for morphological analysis. Western blotting was used to determine the content of PRCP and ERK1/2 in the targeted tissues. The expression of kallikrein mRNA and CGRP mRNA was detected by RT-PCR in kidney. The content of angiotensionâ…¡and CGRP in plasma and mesentery artery wall were measured by radioimmunoassay.Results: Chronic administration of rutaecarpine (10, 20 or 40mg/kg.day) caused a depressor effect in the 2K1C hypertensive rats. In mesentery artery, treatment with rutaecarpine for 4 weeks significantly increased the lumen diameter and decreased the medium thickness, and also decreased the ratio of media cross-sectional area to lumen area compared with hypertensive rats as well. Compared with sham group rats, the activity of ERK1/2 remarkably increased and the content of PRCP significantly decreased in heart, kidney and mesenteric artery; compared with hypertensive rats, the activity of ERK1/2 remarkably decreased and the content of PRCP significantly increased after treatment with rutaecarpine in heart, kidney and mesenteric artery. The expression of kanllikrein mRNA remarkably reduced in hypertensive rats,compared with sham group rats; After treating with rutaecarpine, the expression of kallikrein mRNA significantly increased. The alteration in BP and mesenteric arteries concomitantly with an increase in the plasma concentration and mRNA expression in dorsal root ganglia of CGRP and decrease angiotensinâ…¡level in the plasma and mesenteric arteries in a dose-dependent manner.Conclussion: The rutaecarpine can decrease SBP and reverse cardiovascular remodeling in the 2K1C hypertensive rats. The mechanism of antihypertensive effect of Rut involve in related mechanism: (1)The activation of PRCP that induced the inaction of angiotensinâ…¡; (2)The activation of prekallikrein and Stimulation of CGRP synthesis and release in the tissues.