Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure.
Endothelin is a potent vasoconstrictor peptide released from endothelial cells capable of producing marked and prolonged increases in arterial pressure. The purpose of this study was to determine whether endothelin alters the sensitivity of arterial baroreceptors. Multifiber baroreceptor activity was recorded from the vascularly isolated, endothelium-denuded carotid sinus in dogs anesthetized with alpha-chloralose. Local exposure of baroreceptors to endothelin at a concentration of 10(-8) M produced vasoconstriction of the carotid sinus as measured with sonomicrometer crystals but did not alter baroreceptor discharge significantly. A higher concentration of endothelin (10(-7) M) markedly suppressed baroreceptor activity, particularly at pressures greater than 100 mmHg (n = 7, P less than 0.05). The magnitude of the decrease in activity was dependent on the duration of exposure to endothelin. Baroreceptor activity measured at carotid pressures of 60, 100, and 200 mmHg averaged 23 +/- 4, 65 +/- 6, and 100 +/- 0% of maximum during control; 38 +/- 12, 61 +/- 9, and 74 +/- 15% after exposure to endothelin (10(-7) M) for 2 min; and 27 +/- 8, 53 +/- 12, and 56 +/- 19% after 12 min, respectively. The suppression of nerve activity with the high dose of endothelin was not accompanied by additional vasoconstriction, suggesting a direct effect of endothelin on nerve endings. We speculate that endothelin released from endothelial cells may act in a paracrine manner to suppress activity of baroreceptors, particularly at high levels of arterial pressure. Such an action would interfere with the buffering capacity of the baroreflex and promote hypertension.
Chapleau
M W
MW
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Hajduczok
G
G
Abboud
F M
FM
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002346:Carotid Sinus / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009424:Nervous System Physiological Phenomena; D009994:Osmolar Concentration; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology*
D016232:Endothelins