title: EndothelinB receptors in rabbit pulmonary resistance arteries: effect of left ventricular dysfunction.
abstract: The endothelin (ET) receptor that mediates vasoconstriction of the isolated rabbit pulmonary resistance artery was characterized using selective ET receptor agonists and antagonists. We also examined changes in ET-induced vasoconstriction brought about by left ventricular dysfunction using the rabbit coronary ligation model. The rank order of potency for contraction was sarafotoxin S6c (S6c) > ET-1 = ET-3, which is characteristic of an ETB-like receptor. The combined ETA/ETB receptor antagonist SB209670 (1 microM) antagonized responses to ET-1 and S6c with estimated pKb values of 6.8 +/- 0.2 and 7.8 +/- 0.2, respectively. BQ788 (1 microM) antagonized responses to S6c and ET-3 (but not ET-1) with estimated pKb values of 7.1 +/- 0.2 and 6.6 +/- 0.1, respectively. The ETA receptor antagonist FR139317 (1 microM), either alone or in combination with BQ788, did not inhibit responses to ET-1. The profile of the ET-1 response was not altered by left ventricular dysfunction. In control rabbits, the inhibitor of nitric oxide synthase N omega-nitro-L-arginine methyl ester (100 microM) had no significant effect on the potency of either ET-1 or S6c. In the coronary-ligated rabbits, however, it significantly increased the potency (10-15-fold) of both ET-1 and S6c. These results suggest that the ET receptor that mediates contraction in rabbit pulmonary resistance arteries has the characteristics of an ETB-like receptor. The responses to ET-1 are not altered by LVD but may be modified by increased release of nitric oxide.
authors.affiliation: Division of Neuroscience and Biomedical EC50 Systems, University of Glasgow, Scotland.
authors.forename: C C
authors.initials: CC
authors.lastname: Docherty
authors.forename: M R
authors.initials: MR
authors.lastname: MacLean
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000503:physiopathology*; D011817:Rabbits; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
chemical_list: D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D012701:Serotonin; D011189:Potassium Chloride; D019331:NG-Nitroarginine Methyl Ester