期刊
HYPERTENSION
卷 41, 期 1, 页码 50-55出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.HYP.0000042427.05390.5C
关键词
renin-angiotensin system; mice; vasculature; remodeling; hypertrophy; hypertension, chronic
资金
- NHLBI NIH HHS [HL-22149, HL-62984] Funding Source: Medline
- NINDS NIH HHS [NS-24621] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL022149, P01HL062984] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P01NS024621] Funding Source: NIH RePORTER
We examined the hypothesis that the renin-angiotensin system plays an important role in vascular remodeling (defined as reduced external diameter) during chronic hypertension. We measured pressure, diameter, and cross-sectional area of the vessel wall in maximally dilated cerebral arterioles in transgenic mice that overexpress both human renin and human angiotensinogen and in spontaneously hypertensive mice, a model of chronic hypertension that is thought to develop independently of the renin-angiotensin system. Systemic arterial pressure under conscious conditions was increased by similar amounts in transgenically hypertensive mice (153 +/- 6 versus 117 +/- 4 mmHg in controls; mean +/- SE, P<0.05) and spontaneously hypertensive mice (148 +/- 5 versus 112 +/- 5 mm Hg; P<0.05). The external diameter of maximally dilated cerebral arterioles was reduced in transgenically hypertensive mice (52 +/- 2 versus 66 +/- 3 mum; P<0.05), but not in spontaneously hypertensive mice (58 +/- 4 versus 60 +/- 4 μm; P>0.05). The cross-sectional area of the vessel wall was increased in both transgenically hypertensive mice (504 +/- 53 versus 379 +/- 37 mum(2); P<0.05) and spontaneously hypertensive mice (488 +/- 40 versus 328 +/- 38 μm(2); P<0.05). During maximal dilatation, the stress-strain curves in cerebral arterioles of transgenically hypertensive mice and spontaneously hypertensive mice were shifted to the right of the curves in corresponding controls, an indication that arteriolar distensibility was increased in the transgenically and spontaneously hypertensive groups. Thus, cerebral arterioles undergo remodeling and hypertrophy in transgenically hypertensive mice, but only hypertrophy in spontaneously hypertensive mice. These findings support the hypothesis that the renin-angiotensin system is an important determinant of vascular remodeling during chronic hypertension.
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