title: The vasodilator potency of the endothelium-derived relaxing factor, L-S-nitrosocysteine, is impaired in conscious spontaneously hypertensive rats.
abstract: OBJECTIVE
  This study compared the hemodynamic responses elicited by the endothelium-derived relaxing factor (EDRF), L-S-nitrosocysteine (L-SNC), the non-prostanoid EDRF released by acetylcholine (ACh) and nitric oxide (NO)-donors such as MAHMA NONOate, in conscious spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats.
  
  
  METHODS
  The depressor and/or vasodilator responses elicited by intravenous injections of ACh, L-SNC and MAHMA NONOate were determined in adult WKY and SH rats before and after intravenous injection of the NO synthesis inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), or the cyclooxygenase inhibitor, indomethacin.
  
  
  RESULTS
  The responses elicited by ACh and L-SNC were smaller in SH than in WKY rats whereas the responses elicited by MAHMA NONOate were augmented in SH rats. The ACh-induced responses were not diminished after injection of L-NAME in WKY or SH rats. Indomethacin did not affect the responses to any of the vasodilator agents in WKY or SH rats. Addition of L-SNC to whole blood or thoracic aortae from SH rats yielded similar amounts of NO to those of WKY rats.
  
  
  CONCLUSIONS
  The vasodilator potencies of ACh and L-SNC were diminished whereas that of NO was augmented in SH rats. The loss of potency of L-SNC in SH rats was not obviously due to differences in decomposition to NO or the overactivity of cyclooxygenase factors. This study provides the first evidence that diminished endothelium-dependent vasodilation in SH rats may involve a loss of vasodilator potency of endogenous L-SNC.
authors.affiliation: Department of Physiology and Pharmacology, Institute of Comparative Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7389, USA. slewis@vet.uga.edu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
authors.forename: Maleka P
authors.initials: MP
authors.lastname: Hashmi-Hill
authors.forename: Joy R
authors.initials: JR
authors.lastname: Owen
authors.forename: Kevin
authors.initials: K
authors.lastname: Sandock
authors.forename: Tom P
authors.initials: TP
authors.lastname: Robertson
authors.forename: James N
authors.initials: JN
authors.lastname: Bates
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D003065:Coenzyme A / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D026403:S-Nitrosothiols / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C084625:S-nitroso-coenzyme A; C021315:S-nitrosocysteine; D019001:Nitric Oxide Synthase; D003545:Cysteine; D000109:Acetylcholine; D003065:Coenzyme A; D019331:NG-Nitroarginine Methyl Ester