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OtherPULMONARY PHARMACOLOGY

EndothelinB Receptors in Rabbit Pulmonary Resistance Arteries: Effect of Left Ventricular Dysfunction

Cheryl C. Docherty and Margaret R. Maclean
Journal of Pharmacology and Experimental Therapeutics March 1998, 284 (3) 895-903;
Cheryl C. Docherty
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Margaret R. Maclean
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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 μM) antagonized responses to ET-1 and S6c with estimated pKb values of 6.8 ± 0.2 and 7.8 ± 0.2, respectively. BQ788 (1 μM) 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 μM), 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 synthaseNω-nitro-L-arginine methyl ester (100 μM) 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.

Footnotes

  • Send reprint requests to: Dr. M.R. MacLean, Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, Scotland.

  • ↵1 This work was funded by the Medical Research Council, UK.

  • Abbreviations:
    ET
    endothelin
    ET-1
    endothelin-1
    ET-3
    endothelin-3
    PRA
    pulmonary resistance artery
    S6c
    sarafotoxin S6c
    LVD
    left ventricular dysfunction
    NO
    nitric oxide
    NOS
    nitric oxide synthase, eNOS, endothelial NOS
    L-NAME
    Nω-nitro-L-arginine methyl ester
    PHT
    pulmonary hypertension
    CCRC
    cumulative concentration response curve
    SNP
    sodium nitroprusside
    • Received June 16, 1997.
    • Accepted November 13, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 3
1 Mar 1998
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OtherPULMONARY PHARMACOLOGY

EndothelinB Receptors in Rabbit Pulmonary Resistance Arteries: Effect of Left Ventricular Dysfunction

Cheryl C. Docherty and Margaret R. Maclean
Journal of Pharmacology and Experimental Therapeutics March 1, 1998, 284 (3) 895-903;

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OtherPULMONARY PHARMACOLOGY

EndothelinB Receptors in Rabbit Pulmonary Resistance Arteries: Effect of Left Ventricular Dysfunction

Cheryl C. Docherty and Margaret R. Maclean
Journal of Pharmacology and Experimental Therapeutics March 1, 1998, 284 (3) 895-903;
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