title: Different patterns of H2S/NO activity and cross-talk in the control of the coronary vascular bed under normotensive or hypertensive conditions.
abstract: Hydrogen sulfide (H2S) and nitric oxide (NO) play pivotal roles in the cardiovascular system. Conflicting results have been reported about their cross-talk. This study investigated their interplays in coronary bed of normotensive (NTRs) and spontaneously hypertensive rats (SHRs). The effects of H2S- (NaHS) and NO-donors (sodium nitroprusside, SNP) on coronary flow (CF) were measured in Langendorff-perfused hearts of NTRs and SHRs, in the absence or in the presence of propargylglycine (PAG, inhibitor of H2S biosynthesis), L-NAME (inhibitor of NO biosynthesis), ODQ (inhibitor of guanylate cyclase), L-Cysteine (substrate for H2S biosynthesis) or L-Arginine (substrate for NO biosynthesis). In NTRs, NaHS and SNP increased CF; their effects were particularly evident in Angiotensin II (AngII)-contracted coronary arteries. The dilatory effects of NaHS were abolished by L-NAME and ODQ; conversely, PAG abolished the effects of SNP. In SHRs, high levels of myocardial ROS production were observed. NaHS and SNP did not reduce the oxidative stress, but produced clear increases of the basal CF. In contrast, in AngII-contracted coronary arteries of SHRs, significant hyporeactivity to NaHS and SNP was observed. In SHRs, the vasodilatory effects of NaHS were only modestly affected by L-NAME and ODQ; PAG poorly influenced the effects of SNP. Then, in NTRs, the vascular actions of H2S required NO and vice versa. By contrast, in SHRs, the H2S-induced actions scarcely depend on NO release; as well, the NO effects are largely H2S-independent. These results represent the first step for understanding pathophysiological mechanisms of NO/H2S interplays under both normotensive and hypertensive conditions.
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: L
authors: L
authors: Testai
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: V
authors: V
authors: D'Antongiovanni
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: I
authors: I
authors: Piano
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: A
authors: A
authors: Martelli
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: V
authors: V
authors: Citi
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55. I-56126 Pisa, Italy.
authors: E
authors: E
authors: Duranti
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55. I-56126 Pisa, Italy.
authors: A
authors: A
authors: Virdis
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 55. I-56126 Pisa, Italy.
authors: C
authors: C
authors: Blandizzi
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: C
authors: C
authors: Gargini
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy.
authors: M C
authors: MC
authors: Breschi
authors: Department of Pharmacy, University of Pisa, Via Bonanno, 6. I-56126 Pisa, Italy. Electronic address: calderone@farm.unipi.it.
authors: V
authors: V
authors: Calderone
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism* / Q000494:pharmacology; D006973:Hypertension; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D009599:Nitroprusside; D009569:Nitric Oxide; D006862:Hydrogen Sulfide
keywords: Coronary vessels; Hydrogen sulfide; Hypertension; Nitric oxide