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1 Physiology, Universidad Autonoma de Madrid, Madrid, Madrid, Spain
2 Pharmacology, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Physiology, Universidad Autonoma de Madrid, Madrid, Madrid, Spain
3 Autonomic Physiology Unit, University of Glasgow, Glasgow, United Kingdom
4 Pharmacology, Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain
5 Biochemistry, University of Texas Health Center at Tyler, Tyler, Texas, United States
* To whom correspondence should be addressed. E-mail: silvia.arribas{at}uam.es.
Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hypertension, but their origin is not completely understood. In mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR) we have shown that inward remodeling is associated with abnormal elastic fiber organization leading to smaller fenestrae in the internal elastic lamina (IEL). Our current aim is to determine if this alteration is an early event that precedes vessel narrowing, or if elastic fiber reorganization in SHR arteries occurs because of the remodeling process itself. Using MRA from 10-day, 30-day and 6-month old SHR and normotensive WKY rats, we investigated the time-course of the development of structural and mechanical alterations (pressure myography), elastic fiber organization (confocal microscopy) and amount of elastin (radioimmunoassay for desmosine) and collagen (picrosirius red). SHR MRA had an impairment of fenestrae enlargement during the first month of life. In 30-day old SHR, smaller fenestrae and more packed elastic fibers in the IEL were paralleled by increased wall stiffness. Collagen and elastin levels were unaltered at this age. MRA from 6-month old SHR also had smaller fenestrae and a denser network of adventitial elastic fibers, accompanied by increased collagen content and vessel narrowing. At this age, elastase digestion was less effective in SHR MRA suggesting a lower susceptibility of elastic fibers to enzymatic degradation. These data suggest that abnormal elastic fiber deposition in SHR increases resistance artery stiffness at an early age, which might participate in vessel narrowing later in life.
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