title: S-nitrosothiols dilate the mesenteric artery more potently than the femoral artery by a cGMP and L-type calcium channel-dependent mechanism.
abstract: S-nitrosothiols (SNOs) are metabolites of NO with potent vasodilatory activity. Our previous studies in sheep indicated that intra-arterially infused SNOs dilate the mesenteric vasculature more than the femoral vasculature. We hypothesized that the mesenteric artery is more responsive to SNO-mediated vasodilation, and investigated various steps along the NO/cGMP pathway to determine the mechanism for this difference. In anesthetized adult sheep, we monitored the conductance of mesenteric and femoral arteries during infusion of S-nitroso-l-cysteine (L-cysNO), and found mesenteric vascular conductance increased (137 ± 3%) significantly more than femoral conductance (26 ± 25%). Similar results were found in wire myography studies of isolated sheep mesenteric and femoral arteries. Vasodilation by SNOs was attenuated in both vessel types by the presence of ODQ (sGC inhibitor), and both YC-1 (sGC agonist) and 8-Br-cGMP (cGMP analog) mediated more potent relaxation in mesenteric arteries than femoral arteries. The vasodilatory difference between mesenteric and femoral arteries was eliminated by antagonists of either protein kinase G or L-type Ca(2+) channels. Western immunoblots showed a larger L-type Ca(2+)/sGC abundance ratio in mesenteric arteries than in femoral arteries. Fetal sheep mesenteric arteries were more responsive to SNOs than adult mesenteric arteries, and had a greater L-Ca(2+)/sGC ratio (p = 0.047 and r = -0.906 for correlation between Emax and L-Ca(2+)/sGC). These results suggest that mesenteric arteries, especially those in fetus, are more responsive to SNO-mediated vasodilation than femoral arteries due to a greater role of the L-type calcium channel in the NO/cGMP pathway.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Taiming
authors.initials: T
authors.lastname: Liu
authors.affiliation: Center for Perinatal Biology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Hobe J
authors.initials: HJ
authors.lastname: Schroeder
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Center for Perinatal Biology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
authors.affiliation: Department of Respiratory Care, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Terry
authors.affiliation: Center for Perinatal Biology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Longo
authors.affiliation: Center for Perinatal Biology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University, Loma Linda, CA 92350, USA; Center for Perinatal Biology, Loma Linda University, Loma Linda, CA 92350, USA. Electronic address: ablood@llu.edu.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D005333:Fetus / Q000098:blood supply; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D026422:S-Nitrosoglutathione / Q000494:pharmacology; D026403:S-Nitrosothiols / Q000494:pharmacology*; D012756:Sheep; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007191:Indazoles; D010069:Oxadiazoles; D011810:Quinoxalines; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D026422:S-Nitrosoglutathione; C021315:S-nitrosocysteine; D000071756:Soluble Guanylyl Cyclase; D004110:Diltiazem; D006152:Cyclic GMP; D009543:Nifedipine; D003545:Cysteine
keywords: Fetus; L-type calcium channel; NO/cGMP pathway; S-nitrosothiol; Sheep