RT Journal Article
T1 Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin
A1 Xavier, F. E.
A1 Aras López, R.
A1 Arroyo Villa, I.
A1 Del Campo Milán, Lara
A1 Salaices, M.
A1 Rossoni, L. V.
A1 Ferrer, M.
A1 Balfagón, G.
AB Background and purpose: The present study was designed to assess whether cyclooxygenase-2 (COX-2) activation is involved in the effects of chronic aldosterone treatment on endothelial function of mesenteric resistance arteries (MRA) from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR).Experimental approach: Relaxation to acetylcholine was measured in MRA from both untreated and aldosterone-treated strains. Vasomotor responses to prostacyclin and U46619 were also analysed. Release of 6-oxo-prostaglandin (PG)F1alpha and thromboxane B2 (TxB2) was determined by enzyme immunoassay. COX-2 protein expression was measured by western blot.Key results: Aldosterone reduced acetylcholine relaxation in MRA from both strains. In MRA from both aldosterone-treated strains the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively), TxA2 synthesis inhibitor (furegrelate), prostacyclin synthesis inhibitor (tranylcypromine) or TxA2/ PGH2 receptor antagonist (SQ 29 548), but not COX-1 inhibitor SC-560, increased acetylcholine relaxation. In untreated rats this response was increased only in SHR. Prostacyclin elicited a biphasic vasomotor response: lower concentrations elicited relaxation, whereas higher concentrations elicited contraction that was reduced by SQ 29 548. Aldosterone increased the acetylcholine-stimulated production of 6-oxo-PGF(1alpha) and TxB2 in MRA from both strains. COX-2 expression was higher in both strains of rats treated with aldosterone.Conclusions and implications: Chronic treatment with aldosterone impaired endothelial function in MRA under normotensive and hypertensive conditions by increasing COX-2-derived prostacyclin and thromboxane A2. As endothelial dysfunction participates in the pathogenesis of many cardiovascular disorders we hypothesize that anti-inflammatory drugs, specifically COX-2 inhibitors, could ameliorate vascular damage in patients with elevated aldosterone production.
PB Wiley
SN 0007-1188
YR 2008
FD 2008-05-26
LK https://hdl.handle.net/20.500.14352/97807
UL https://hdl.handle.net/20.500.14352/97807
LA eng
NO Xavier FE, Aras-López R, Arroyo-Villa I, del Campo L, Salaices M, Rossoni LV, Ferrer M, Balfagón G. Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin. Br J Pharmacol. 2008 Jul;154(6):1225-35
NO Ministerio de Sanidad (España)
NO Comisión de Ciencia y Tecnología (España)
NO Banco de Santander/Universidad Autónoma de Madrid (España)
DS Docta Complutense
RD 7 abr 2025