title: ACE inhibition restores the vasodilator potency of the endothelium-derived relaxing factor, L-S-nitrosocysteine, in conscious Spontaneously Hypertensive rats.
abstract: OBJECTIVE
  The major aim of this study was to determine whether the angiotensin converting enzyme (ACE) inhibitors, captopril or enalapril, restore the diminished vasodilator potency of the endothelium-dependent agonist, acetylcholine (ACh), and the endothelium-derived relaxing factor (EDRF), L-S-nitrosocysteine (L-SNC), in conscious Spontaneously Hypertensive (SH) rats.
  
  
  METHODS
  The hemodynamic responses elicited by i.v. injections of ACh, L-SNC, and nitric oxide donors such as MAHMA NONOate, were determined in SH rats treated for 7 days with captopril, enalapril, or the direct vasodilator hydralazine. The effects of captopril, enalapril or hydralazine on oxidant stress levels in blood serum and aorta of WKY and SH rats were also determined.
  
  
  RESULTS
  Captopril, enalapril and hydralazine elicited equivalent falls in mean arterial pressure and systemic vascular resistances in SH rats. ACh- and L-SNC-induced vasodilation were increased in captopril- or enalapril-treated SH rats such that the responses were equal to those in normotensive Wistar Kyoto rats. The attenuated responses of ACh and L-SNC in SH rats were not improved by hydralazine. The vasodilator effects of MAHMA NONOate, which were substantially augmented in SH rats, were not affected by captopril, enalapril or hydralazine. The levels of oxidant stress were markedly reduced in captopril- or enalapril-treated but not hydralazine-treated SH rats.
  
  
  CONCLUSIONS
  The finding that the ACE inhibitors improved the vasodilator potencies of L-SNC and the EDRF released by ACh in SH rats, suggests that the diminished vasodilator potency of these compounds was due to augmented ACE activity, which increased oxidant stress levels. This study provides the first evidence to support the concept that ACE inhibition lowers arterial pressure in SH rats, at least in part, by restoring the vasodilator potency of endothelium-derived 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; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure; D002216:Captopril / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects* / Q000503:physiopathology; D019803:Glutathione Disulfide / Q000097:blood / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D026403:S-Nitrosothiols / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020030:Nitric Oxide Donors; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D006830:Hydralazine; C075750:8-epi-prostaglandin F2alpha; D004656:Enalapril; C021315:S-nitrosocysteine; D002216:Captopril; D015237:Dinoprost; D003545:Cysteine; D000109:Acetylcholine; D019803:Glutathione Disulfide