Abstract

Background

To study the effects of prehypertensive losartan treatment on blood pressure, resistance vessel remodeling, and angiotensin II type 1 receptor (AT1R) expression in adult spontaneously hypertensive rats (SHRs).

Methods

Four-week-old SHR and Wistar-Kyoto rats were randomly divided into losartan-treated and untreated groups. Losartan was administrated by gavage from 4 to 10 weeks old. Blood pressure was monitored by the tail-cuff method till 26 weeks old. The third grade mesenteric arteries were then isolated. Vessel structure, relaxation reactivity, angiotensin II type 1 receptor expression, and angiotensin II levels were analyzed.

Results

Losartan treatment from 4 to 10 weeks of age significantly lowered systolic blood pressure from 10 to 26 weeks in SHR. At 26 weeks old, wall thickness to lumen radius and wall area to lumen area of mesenteric arteries were significantly lower in losartan-treated than untreated SHR (P < 0.01). Maximum relaxation to acetylcholine and its pD2 were increased in losartan-treated compared to untreated SHR (P < 0.01). Angiotensin II type 1 receptor mRNA and protein levels were significantly reduced in losartan-treated SHR (P < 0.01). However, angiotensin II levels in plasma and mesenteric arteries of losartan-treated SHR were higher than those of untreated SHR (P < 0.05). Losartan treatment lowered systolic blood pressure in Wistar-Kyoto at the age of 10 weeks (P < 0.05), but had no significant effect on blood pressure after 14 weeks or mesenteric arteries at 26 weeks.

Conclusions

Blood pressure reduction induced by prehypertensive losartan treatment ameliorates resistance vessel remodeling and downregulates angiotensin II type 1 receptor expression in adult SHR.

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