title: Relevance of endothelium-derived hyperpolarizing factor in the effects of hypertension on rat coronary relaxations.
abstract: OBJECTIVE
  To evaluate the relative participation of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in the relaxing responses induced by acetylcholine and isoproterenol in isolated coronary arteries from adult Wistar- Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).
  
  
  METHODS
  Male adult WKY rats and SHR were used in the study. Segments from left coronary arteries (approximately 350-380 microm internal diameter and 2 mm long) were mounted in an isometric myograph and pre-contracted with serotonin. Dose-response curves to acetylcholine and isoproterenol were carried out in absence and presence of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (LNAME), the inhibitor of the cyclo-oxygenase, indomethacin and KCI. Areas under the respective dose-response curves were used to calculate the approximate relative participation of NO, EDHF and prostanoids.
  
  
  RESULTS
  Relaxations to either acetylcholine or isoproterenol were lower in SHR than in WKY rats. In WKY rats, presence of LNAME diminished (P< 0.05) relaxation to acetylcholine from 10(-9) to 10(-6) mol/l, and induced a contracting response at 10(-5) and 10(-4) mol/l of acetylcholine. Addition of indomethacin did not significantly affect dose-related relaxation to acetylcholine 10(-9) to 10(-6) mol/l in WKY rats, and reduced (P < 0.05) the contracting response observed at 10(-5) mol/l of acetylcholine. In SHR, addition of LNAME markedly reduced (P< 0.05) acetylcholine relaxations, but did not produce any contracting effect. Addition of indomethacin on top of LNAME slightly (P< 0.05) enhanced relaxing response to acetylcholine in SHR. Presence of LNAME in the media diminished (P < 0.05) relaxation to isoproterenol in both WKY rats and SHR. Addition of indomethacin on top of LNAME increased (P< 0.05) isoproterenol-relaxing response to levels similar to and higher than control conditions in WKY rats and SHR, respectively. Addition of KCI blunted both acetylcholine- and isoproterenol-relaxations in both groups.
  
  
  CONCLUSIONS
  NO and EDHF are the main endothelium-derived relaxing factors underlying acetylcholine and isoproterenol relaxations in rat coronary arteries, respectively. EDHF reduction, and not only NO reduction play a key role in the diminished coronary relaxations induced by acetylcholine and isoproterenol in SHR. An arachidonic acid derivative with contracting activity released by acetylcholine and isoproterenol in a differential manner, could oppose the relaxing actions of NO and EDHF.
authors.affiliation: Department of Physiology, School of Medicine, Complutense University, Madrid, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Vázquez-Pérez
authors.forename: J
authors.initials: J
authors.lastname: Navarro-Cid
authors.forename: N
authors.initials: N
authors.lastname: de las Heras
authors.forename: E
authors.initials: E
authors.lastname: Cediel
authors.forename: D
authors.initials: D
authors.lastname: Sanz-Rosa
authors.forename: L M
authors.initials: LM
authors.lastname: Ruilope
authors.forename: V
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: V
authors.initials: V
authors.lastname: Lahera
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D007545:Isoproterenol; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester