Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation

Rosa Aras-López , Fabiano E. Xavier , Mercedes Ferrer , Gloria Balfagón (1)

1 Fisiología

Neuronal nitric oxide (NO) plays a functional role in many vascular tissues, including mesenteric arteries (MA). Glucocorticoids alter NO release from endothelium and the central nervous system, but no data from peripheral innervation have been reported. We studied the effects of dexamethasone on electrical field stimulation (EFS)-induced NO release in MA from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and the role of PKC in this response. In endothelium-denuded MA L-NAME increased the contractile response to EFS only in segments from SHR. EFS-induced contraction was reduced by 1 µmol/L of dexamethasone in segments from SHR but not WKY and this effect was abolished in presence of dexamethasone. EFS induced a tetrodotoxin-resistant NO release in WKY MA, which remained unchanged by 1 µmol/L of dexamethasone. In SHR MA, dexamethasone decreased basal and EFS-induced neuronal NO release and this decrease was prevented by the glucocorticoid receptor antagonist, mifepristone. Dexamethasone did not affect nNOS expression in either strain. In SHR MA, incubation with calphostin C (non-selective PKC inhibitor), Gö6983 (classic, δ, and ζ PKC inhibitor), LY379196 (PKCβ inhibitor), or PKCζ-PI (PKCζ inhibitor) decreased both basal and EFS-induced neuronal NO release. Additionally, PKC activity was reduced by dexamethasone. The PKC inhibitor-induced reduction in NO release was unaffected by dexamethasone. In conclusion, results obtained here indicate that PKC activity positively modulates the neuronal NO release in MAs from SHR. They also reveal that by PKC inhibition, through activation of glucocorticoid receptors, dexamethasone reduces neuronal NO release in these arteries.

Mots clés: Medicine

Rosa Aras-López, Fabiano E. Xavier, Mercedes Ferrer, Gloria Balfagón. Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation. Clinical Science, 2009, 117 (8), pp.305-312. ⟨10.1042/CS20080178⟩. ⟨hal-00511186⟩