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Dependence of the endothelin‐mediated pressor response on neuronal ET B ‐mediated neurotransmitter release in sl/sl rats
Author(s) -
D’Angelo Gerard,
Middleton Christopher,
Pollock David M.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a886-b
Subject(s) - endocrinology , medicine , prazosin , endothelin receptor , agonist , chemistry , adrenergic antagonist , neurotransmitter , receptor , stimulation , endothelin 3 , receptor antagonist , endothelin 1 , antagonist , endothelins
Stimulation of endothelin B (ET B ) receptors can increase neuronal oxidative stress, and consequently sympathetic nerve activity. Therefore we tested the hypothesis that the pressor response to ET‐1 is partially mediated by the ET B receptor‐mediated release of constrictor neurotransmitters from perivascular nerves. Pressor responses to the selective ET B receptor agonist sarafotoxin (S6c) were examined in anesthetized female, wild‐type (WT) and ET B receptor‐deficient ( sl/sl ) rats during ganglion blockade. S6c produced dose‐dependent increases in arterial pressure in both WT and sl/sl rats. In WT rats, pretreatment with the selective α 1 adrenergic antagonist prazosin (1 mg/kg) had no effect on the pressor response. Conversely, in sl/sl rats, S6c caused a maintained depressor response to 0.3 and 1.0 nmol/kg S6c (steady state: −7±3 and −11±3 mmHg @ 0.3 and 1.0 nmol/kg, respectively) in the presence of prazosin. Pressor responses were restored, however, by the combination of α 1 and β adrenergic (propranolol; 5 mg/kg) blockade (peak: 12±2, 11±1, and 16±4 mmHg @ 0.1, 0.3, and 1.0 nmol/kg, respectively). Because functional ET B receptors are expressed only in neuronal tissue in sl/sl rats, these data suggest that responses to S6c are achieved by the ET B receptor‐dependent release of neurotransmitters from perivascular nerves, including a yet unidentified non‐adrenergic vasoconstrictor neurotransmitter(s).