title: Activation of neuronal endothelin B receptors mediates pressor response through alpha-1 adrenergic receptors.
abstract: Abnormalities in activity of the endothelin (ET) system have been widely reported in a number of cardiovascular disease states such as hypertension and heart failure. Although the vascular responses to ET are well established, the interaction between ET and other important modulators of blood pressure, such as the sympathetic nervous system, are less understood. Previous reports implicate ET signaling through ET type B (ETB) receptors in increasing neuronal activity. Therefore, we hypothesized that activation of ETBreceptors on sympathetic nerves would increase blood pressure through an adrenergic-mediated mechanism. Thus, we used anesthetized ETB-deficient rats, which only express functional ETBreceptors on adrenergic neurons, and genetic controls, which express functional ETBreceptors in vascular tissue and kidney epithelium. We determined the pressor response to the selective ETBreceptor agonist sarafotoxin c (S6c). Separate groups of rats were treated with theα1-adrenergic receptor antagonist prazosin or theβ-adrenergic receptor antagonist propranolol to elucidate the role of adrenergic signaling in mediating the blood pressure response. We observed a dose-dependent pressor response to S6c in ETB-deficient rats that was reversed by prazosin treatment and augmented by propranolol. In genetic control rats, the effects of S6c on sympathetic neurons were mostly masked by the direct activity of ETBreceptor activation on the vasculature. Heart rate was mostly unaffected by S6c across all groups and treatments. These results suggest that ETBactivation on sympathetic neurons causes an increase in blood pressure mediated throughα1-adrenergic receptor signaling.
authors.affiliation: Division of Nephrology, Department of Medicine, Cardio-Renal Physiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Becker
authors.affiliation: Division of Nephrology, Department of Medicine, Cardio-Renal Physiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Speed
authors.affiliation: Division of Nephrology, Department of Medicine, Cardio-Renal Physiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Mackenzie
authors.initials: M
authors.lastname: Powell
authors.affiliation: Division of Nephrology, Department of Medicine, Cardio-Renal Physiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama davidpollock@uabmc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D055647:Rats, Transgenic; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D044023:Receptor, Endothelin B; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D011433:Propranolol; D011224:Prazosin
keywords: Blood pressure; hypertension; sympathetic nerves