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- Title
Aldosterone induces endothelial dysfunction in resistance arteries from normotensive and hypertensive rats by increasing thromboxane A2 and prostacyclin.
- Authors
Xavier, F. E.; Aras-López, R.; Arroyo-Villa, I.; del Campo, L.; Salaices, M.; Rossoni, L. V.; Ferrer, M.; Balfagón, G.; Aras-López, R; Balfagón, G
- Abstract
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)F1α 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-PGF1α 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.British Journal of Pharmacology (2008) 154, 1225–1235; doi:10.1038/bjp.2008.200; published online 26 May 2008
- Subjects
HYPERTENSION; ALDOSTERONE; ARTERIES; PROSTACYCLIN; MESENTERIC artery; THROMBOXANES; PROSTAGLANDINS; IN vitro studies; VASOCONSTRICTORS; RESEARCH; ENDOTHELIUM; MUSCLE contraction; POTASSIUM chloride; SMOOTH muscle; WESTERN immunoblotting; ANIMAL experimentation; NORADRENALINE; RESEARCH methodology; MEDICAL cooperation; EVALUATION research; RATS; VASCULAR resistance; COMPARATIVE studies; VASCULAR diseases; OXIDOREDUCTASES; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2008, Vol 154, Issue 6, p1225
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.200