title: Endothelin-1-induced elevation in blood pressure is independent of increases in sympathetic nerve activity in normotensive rats.
abstract: This study was performed to determine if endothelin-1 (ET-1)-induced pressor responses in urethane-anesthetized, normotensive rats are due to increased sympathetic nerve activity. Renal sympathetic nerve activity (RSNA) was used as an index of sympathetic nerve activity. ET-1 (30- 1000 pmol/kg) or sarafotoxin (S6c, ET B receptor agonist, 10-3,000 nmol/kg) given by bolus injection produced transient decreases in mean arterial pressure (MAP) and increases in RSNA and heart rate (HR). ET-1 caused a delayed but sustained increase in MAP that was not inhibited by acute sinoaortic denervation or alpha 1 -adrenergic receptor blockade. ET-1 never caused a sustained change in HR or RSNA. A-192621 (ET B receptor antagonist, 12 mg/kg) increased MAP (10-20 mm Hg) and decreased HR and RSNA. A-192621 blocked the transient decrease in MAP and increase in RSNA and HR caused by ET-1 and S6c. In A-192621-treated rats, ET-1, but not S6c, caused a sustained increase in MAP and decrease in HR and RSNA. After A-192621 treatment, ET-1 infusion caused a sustained elevation in MAP; HR and RSNA decreased only after the highest ET-1 dose. These results indicate that the initial increase in RSNA after ET-1 or S6c is secondary to ET B receptor-mediated vasodilation. Increased RSNA does not contribute to ET-1-induced pressor responses; these responses are likely due to vasoconstriction in normotensive, anesthetized rats. Finally, baroreceptor reflexes function after ET-1 or S6c treatment.
authors.affiliation: Department of Pharmacology, Michigan State University, East Lansing, Michigan 48824, USA. xuhui2@msu.edu
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: G D
authors.initials: GD
authors.lastname: Fink
authors.forename: J J
authors.initials: JJ
authors.lastname: Galligan
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D010656:Phenylephrine; D011224:Prazosin