AT(1) receptor inhibition does not reduce arterial wall hypertrophy or PDGF-A expression in renal hypertension

To separate the role of ANG II from pressure in hypertrophy of the vascular wall in one-kidney, one-clip (1K1C) hypertension, experimental and sham-operated rats were given the AT(1)-receptor antagonist losartan (20 mg x kg(-1) x day(-1)) or tap water for 14 days. Mean arterial pressure was elevated...

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Veröffentlicht in:American journal of physiology. Heart and circulatory physiology 2000-02, Vol.278 (2), p.H613-H622
Hauptverfasser: Parker, S B, Dobrian, A D, Wade, S S, Prewitt, R L
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Sprache:eng
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Zusammenfassung:To separate the role of ANG II from pressure in hypertrophy of the vascular wall in one-kidney, one-clip (1K1C) hypertension, experimental and sham-operated rats were given the AT(1)-receptor antagonist losartan (20 mg x kg(-1) x day(-1)) or tap water for 14 days. Mean arterial pressure was elevated in both experimental groups compared with controls. Rats were anesthetized with pentobarbital sodium, and the thoracic aorta and carotid, small mesenteric, and external spermatic arteries were harvested and embedded in paraffin. Tissue sections were used for morphological analysis, immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and platelet-derived growth factor (PDGF)-AA, stereological measurements, and in situ hybridization with a (35)S-labeled riboprobe for PDGF-A mRNA. Elevated cross-sectional areas of thoracic, carotid, and small mesenteric artery in 1K1C rats were not reduced by losartan. The internal diameter of the external spermatic artery and microvascular density of the cremaster muscle were reduced in 1K1C rats. The number of BrdU-positive nuclei per cross section did not differ between 1K1C and control arteries. PDGF-A mRNA was elevated in the arterial walls of 1K1C rats compared with controls and was hardly changed by losartan. PDGF-A protein stained strongly in the media of 1K1C arteries and was not inhibited by losartan; it appeared in the adventitia of all aortas and carotid arteries. These observations demonstrate that effects of ANG II mediated through the AT(1) receptor are not necessary for hypertrophy of the vascular wall during 1K1C hypertension or expression of PDGF-A.
ISSN:0363-6135
DOI:10.1152/ajpheart.2000.278.2.H613