title: Hydrogen sulfide is involved in dexamethasone-induced hypertension in rat.
abstract: Glucocorticoid (GC)-induced hypertension is a common clinical problem still poorly understood. The presence of GC receptor (GR) in vascular smooth muscle and endothelial cells suggests a direct role for GC in vasculature. In response to hemodynamic shear stress, endothelium tonically releases nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF) and prostacyclin contributing to vascular homeostasis. Recently, hydrogen sulfide (H2S) has been proposed as a candidate for EDHF. H2S is endogenously mainly formed from L-cysteine by the action of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). It plays many physiological roles and contributes to cardiovascular function. Here we have evaluated the role played by H2S in mesenteric arterial bed and in carotid artery harvested from rats treated with vehicle or dexamethasone (DEX; 1.5 mg/kg/day) for 8 days. During treatments systolic blood pressure was significantly increased in conscious rats. EDHF contribution was evaluated in ex-vivo by performing a concentration-response curve induced by acetylcholine (Ach) in presence of a combination of indomethacin and L-NG-Nitroarginine methyl ester in both vascular districts. EDHF-mediated relaxation was significantly reduced in DEX-treated group in both mesenteric bed and carotid artery. EDHF-mediated relaxation was abolished by pre-treatment with both apamin and charybdotoxin, inhibitors of small and big calcium-dependent potassium channels respectively, or with propargylglycine, inhibitor of CSE. Western blot analysis revealed a marked reduction in CBS and CSE expression as well as H2S production in homogenates of mesenteric arterial bed and carotid artery from DEX-treated rats. In parallel, H2S plasma levels were significantly reduced in DEX group compared with vehicle. In conclusion, an impairment in EDHF/H2S signaling occurs in earlier state of GC-induced hypertension in rats suggesting that counteracting this dysfunction may be beneficial to manage DEX-associated increase in blood pressure.
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: d'Emmanuele di Villa Bianca
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: Mitidieri
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Erminia
authors.initials: E
authors.lastname: Donnarumma
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tramontano
authors.affiliation: Department of Science, University of Basilicata, Via dell'Ateneo Lucano, 85100 Potenza, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brancaleone
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy. Electronic address: cirino@unina.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Bucci
authors.affiliation: Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, 80131 Naples, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Sorrentino
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002339:Carotid Arteries / Q000737:chemistry / Q000187:drug effects; D003907:Dexamethasone / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D003907:Dexamethasone; D006862:Hydrogen Sulfide
keywords: Carotid artery; EDHF; Glucocorticoid-induced hypertension; Hydrogen sulfide; Mesentery; Rat