Neuronal NO plays a functional role in many vascular tissues, including MAs (mesenteric arteries). Glucocorticoids alter NO release from endothelium and the CNS (central nervous system), but no results from peripheral innervation have been reported. In the present study we investigated the effects of dexamethasone on EFS (electrical field stimulation)-induced NO release in MAs from WKY (Wistar–Kyoto) rats and SHRs (spontaneously hypertensive rats) and the role of PKC (protein kinase C) in this response. In endothelium-denuded MAs, L-NAME (NG-nitro-L-arginine methyl ester) increased the contractile response to EFS only in segments from SHRs. EFS-induced contraction was reduced by 1 μmol/l dexamethasone in segments from SHRs, but not WKY rats, and this effect was abolished in the presence of dexamethasone. EFS induced a tetrodotoxin-resistant NO release in WKY rat MAs, which remained unchanged by 1 μmol/l dexamethasone. In SHR MAs, 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 [neuronal NOS (NO synthase)] expression in either strain. In SHR MAs, incubation with calphostin C (a non-selective PKC inhibitor), Gö6983 (a classic PKC δ and ζ inhibitor), LY379196 (a PKCβ inhibitor) or PKCζ-PI (PKCζ pseudosubstrate 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 in the present study indicate that PKC activity positively modulates the neuronal NO release in MAs from SHRs. They also reveal that by PKC inhibition, through activation of glucocorticoid receptors, dexamethasone reduces neuronal NO release in these arteries.
Dexamethasone decreases neuronal nitric oxide release in mesenteric arteries from hypertensive rats through decreased protein kinase C activation
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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. Clin Sci (Lond) 1 October 2009; 117 (8): 305–312. doi: https://doi.org/10.1042/CS20080178
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