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Effects of perindopril on vascular wall and left ventricular hypertrophy in rats with experimental hypertension
Insights
Perindopril treatment in hypertensive rats reduced left ventricular and arterial wall hypertrophy. These effects are linked to the tissue renin-angiotensin system, not circulating angiotensin II.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Hypertension Studies
Background:
- Hypertension is a major risk factor for cardiovascular disease, often involving cardiac and vascular remodeling.
- The renin-angiotensin system (RAS) plays a crucial role in regulating blood pressure and vascular function.
- Understanding the tissue-specific effects of antihypertensive drugs is vital for effective treatment.
Purpose of the Study:
- To investigate the effects of perindopril on cardiac and vascular hypertrophy in a rat model of hypertension.
- To explore the role of circulating and tissue-bound angiotensin II in mediating these effects.
- To determine if perindopril's efficacy is related to inhibition of the tissue RAS.
Main Methods:
- Establishment of a hypertensive rat model via abdominal aortic constriction.
- Administration of low-dose (0.1 mg/kg/d) and high-dose (1.5 mg/kg/d) perindopril for 4 weeks.
- Measurement of mean arterial pressure (MAP), heart weight, vascular morphometry, and angiotensin II (A II) levels in plasma and aortic tissue.
Main Results:
- Both low-dose and high-dose perindopril prevented left ventricular hypertrophy and superior mesenteric artery media hypertrophy.
- High-dose perindopril significantly inhibited aortic media hypertrophy.
- Perindopril's beneficial effects correlated with inhibition of the tissue RAS in the vascular wall and heart, independent of plasma A II levels.
Conclusions:
- Perindopril demonstrates protective effects against cardiac and vascular hypertrophy in a rat hypertension model.
- The antihypertensive and tissue-remodeling effects of perindopril are likely mediated by the inhibition of the local tissue renin-angiotensin system.
- Circulating angiotensin II levels do not appear to be the primary mediator of perindopril's observed benefits.
Abstract:
The model of hypertensive rat was established by using the method of abdominal aortic constriction, 33 male SD rats were randomly divided into 4 groups: group A (sham-operated rats serving as controls), group B (hypertensive rats serving as controls), group C (hypertensive rats subjected to low-dose perindopril treatment, 0.1 mg.kg-1/d) and group D (hypertensive rats receiving high-dose perindopril treatment, 1.5 mg.kg-1/d). The drug was administered by gavage for 4 weeks. At the end of the treatment, mean arterious pressure (MAP) was measured via catheter in the carotid artery. The heart was taken and weighed to calculate the ratio of left ventricular weight to body weight (LVW/BW). The ratio of medial mean thickness to mean diameter of lumen of aorta and superior mesenteric artery was calculated by morphometry. Concentration of angiotensin II (A II) in plasma and in aortic wall were determined by radioimmunoassay (PA II, AA II). Our results showed that both high-dose and low-dose perindopril may prevent hypertrophy of left ventricle and hypertrophy of the tunica media of superior mesenteric artery. In addition, high-dose perindopril may significantly inhibit hypertrophy of aortic media. The above effects of perindopril may be explained by inhibition on tissue renin-angiotensin system of both vascular wall and heart, but is not related to circulating A II (PA II).