Received for publication March 30, 2007.
Revised June 8, 2007.
Accepted for publication June 8, 2007.

Dexamethasone decreases contraction to electrical field stimulation in mesenteric arteries from spontaneously hypertensive rats through decreases in TXA₂ release

Abstract

OBJECTIVES: Glucocorticoids play a role in the control of vascular smooth muscle tone through the alteration of vasoconstrictor and vasodilator factor production. We studied the effect of dexamethasone on vasoconstriction induced by electrical field stimulation (EFS) in rat mesenteric arteries (MA) and the role of hypertension in this effect. METHODS: Endothelium-denuded MA were obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). EFS response was analyzed by isometric tension recordings and cyclooxygenase-2 (COX-2) expression by Western blot. Noradrenaline (NA) release was evaluated in segments incubated with [³H]NA. RESULTS: Dexamethasone (0.1 and 1 µM; 2-8 h) reduced vasoconstriction to EFS (200 mA, 0.3 ms, 1-16 Hz), in a dose- and time-dependent manner only in SHR. However, the release of EFS-induced [³H]NA induced by EFS was increased in SHR arteries preincubated with dexamethasone (1 µM; 6 h). The TxA₂ synthase inhibitor furegrelate (10 µM), the selective COX-2 inhibitor NS-398 (10 µM), or the TP receptor antagonist SQ 29548 (1 µM), reduced EFS and NA induced vasoconstrictor responses. However, the effect of these drugs was abolished in arteries preincubated with dexamethasone. Both dexamethasone and phentolamine (1 µM) inhibited the increased TxB₂ levels observed after EFS. COX-2 protein expression was reduced by dexamethasone in SHR arteries. CONCLUSIONS: Results suggest that dexamethasone reduces vasoconstriction to EFS in MA from SHR by decreasing COX-2 expression, which in turn decreases the smooth muscle TXA₂ release induced by -adrenoceptor activation. The undetectable COX-2 expression in MA from normotensive animals explains the non effect of dexamethasone in their arteries.

Key words: dexamethasone, electrical field stimulation, hypertension, mesenteric arteries, noradrenaline release, thromboxane A2 release

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