Vasodilator activity of hydrogen sulfide (H2S) in human mesenteric arteries.
The role of endogenous H2S has been highlighted as a gaseous transmitter. The vascular smooth muscle inhibitory effects of H2S have been characterized in isolated aorta and mesenteric arteries in rats and mice. Our study was aimed at investigating the vascular effects of H2S on human isolated mesenteric arteries and examining the underlying mechanisms involved. All experiments were performed on rings (4-8mm long) of human mesenteric arteries obtained from patients undergoing abdominal surgery. Ethical approval was obtained from the Ethics Committee of the University Hospital of the University of Florence (app. N. 2015/0024947). The effect of NaHS, an H2S donor, was determined using noradrenaline pre-contracted human isolated mesenteric rings. NaHS evoked a concentration-dependent relaxation (EC5057μM). In contrast, homocysteine, an endogenous precursor of H2S, failed to affect human isolated mesenteric rings. Vasorelaxant response to NaHS was reduced by endothelium removal, application of the nitric oxide synthase inhibitor L-NAME and ODQ inhibitor of cyclic GMP. SQ 22536, an adenylate-cyclase inhibitor, failed to block NaHS-induced vasorelaxation. Inhibition of endogenous prostanoid production by indomethacin significantly reduced NaHS induced vasorelaxation. The role of potassium channels was also examined: blockers of the Ca2+-dependent potassium channel, charybdotoxin and apamin, failed to have any influence on the relaxant response to NaHS on this vascular tissue. In summary, H2S induced relaxation of isolated rings of human mesenteric arteries. Endothelium-dependent related mechanisms with the stimulation of ATP-sensitive potassium channels represents important cellular mechanisms for H2S effect on human mesenteric arteries.
Department of Health Sciences, University of Florence, Florence, Italy.
Serena
S
Materazzi
Department of Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy. Electronic address: giovanni.zagli@unifi.it.
Giovanni
G
Zagli
Department of Health Sciences, University of Florence, Florence, Italy.
Romina
R
Nassini
Division of Oncological and Robotic General Surgery, Careggi University Hospital, Florence, Italy.
Ilenia
I
Bartolini
Department of Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy.
Stefano
S
Romagnoli
Department of Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy.
Cosimo
C
Chelazzi
Department of Health Sciences, University of Florence, Florence, Italy.
Silvia
S
Benemei
Division of Oncological and Robotic General Surgery, Careggi University Hospital, Florence, Italy.
Andrea
A
Coratti
Department of Health Sciences, University of Florence, Florence, Italy; Department of Anesthesia and Intensive Care, Careggi University Hospital, Florence, Italy.
Angelo Raffaele
AR
De Gaudio
Department of Corporate Drug Development, Chiesi Farmaceutici SpA, Parma, Italy.
Riccardo
R
Patacchini
D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010069:Oxadiazoles / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011453:Prostaglandins; D011810:Quinoxalines; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide
H(2)S; Human artery; Hydrogen sulfide; Vasodilatation