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Effects and Mechanisms of All-trans Retinoic Acid on Myocardium and Vascular Smooth Muscles in Spontaneously Hypertensive Rats

Author: HuangZhen
Tutor: ZhangQin
School: Third Military Medical University
Course: Journal of Clinical Pharmacology
Keywords: all-trans retinoic acid spontaneous hypertension proliferation of smooth muscles ACE ACE2
CLC: R96
Type: Master's thesis
Year: 2006
Downloads: 94
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Abstract


Backgrounds and Objective:ATRA plays an important role in development and mature of cardiovascular system, in addition, it inhibits proliferation of multi-cells. Recently, its restrictive function on vascular smooth muscle cell (VSMC) has drawn much attention, but whether there was inhibiting effect on proliferation of smooth muscles caused by hypertension is still unknown. Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) are two key enzymes of renin-angiotensin system (RAS) and they have opposite effect in RAS. ACE is a zinc metalloprotease, under the function of which can yield angiotensin II (Ang II) that can occupy the angiotensin receptor. Ang II is a most potent vasoconstrictor, which can induce hypertension and promote cell proliferation. ACE2, a analogue of ACE is also a zinc metalloprotease but with carboxypeptidase’s activity. It can hydrolyze part of Ang II to angiotensin 1-7 (Ang-[1-7]) which is a potent vasodilator peptide. ACE2 neutralizates the vasopressor effect which ACE mediate by Ang II. Therefore, the two enzyme play an important role in pathogenesis、development and sustain of essential hypertension. It is reported that ATRA has effect on regulating the gene expression of components of renin-angiotensin system (RAS), however, whether this role relate to the two enzymes or not and how to react remain uncertain. In view of the effect of ATRA on RAS, this paper investigated the effect of ATRA on the expression of the ACE messenger RNA (mRNA)、ACE2 messenger RNA (mRNA) and proliferating cell nuclear antigen(PCNA), discussed the possible actions of ATRA on the essential hypertension.Methods:Eighteen fifteen-week-old male SHRs were randomly divided into three groups: ATRA-treated group(treated with atRA 10 mg·kg–1·day–1), dissolvant-treated group (treated with dissolvent 1ml·kg–1·day–1) and captopril-treated group (treated with captopril 0.25 mg·. kg–1·day–1). 4 weeks after treatment, the SHRs were anesthetized and took blood through abdominal aorta artery. The aorta and the middle part of the left

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