title: Endothelin-1-induced vasoconstriction does not require intracellular Ca²⁺ waves in arteries from rats exposed to intermittent hypoxia.
abstract: Sleep apnea is associated with cardiovascular disease, and patients with sleep apnea have elevated plasma endothelin (ET)-1 concentrations. Rats exposed to intermittent hypoxia (IH), a model of sleep apnea, also have increased plasma ET-1 concentrations and heightened constriction to ET-1 in mesenteric arteries without an increase in global vascular smooth muscle cell Ca(2+) concentration ([Ca(2+)]). Because ET-1 has been shown to increase the occurrence of propagating Ca(2+) waves, we hypothesized that ET-1 increases Ca(2+) wave activity in mesenteric arteries, rather than global [Ca(2+)], to mediate enhanced vasoconstriction after IH exposure. Male Sprague-Dawley rats were exposed to sham or IH conditions for 7 h/day for 2 wk. Mesenteric arteries from sham- and IH-exposed rats were isolated, cannulated, and pressurized to 75 mmHg to measure ET-1-induced constriction as well as changes in global [Ca(2+)] and Ca(2+) wave activity. A low concentration of ET-1 (1 nM) elicited similar vasoconstriction and global Ca(2+) responses in the two groups. Conversely, ET-1 had no effect on Ca(2+) wave activity in arteries from sham rats but significantly increased wave frequency in arteries from IH-exposed rats. The ET-1-induced increase in Ca(2+) wave frequency in arteries from IH rats was dependent on phospholipase C and inositol 1,4,5-trisphosphate receptor activation, yet inhibition of phospholipase C and the inositol 1,4,5-trisphosphate receptor did not prevent ET-1-mediated vasoconstriction. These results suggest that although ET-1 elevates Ca(2+) wave activity after IH exposure, increases in wave activity are not associated with increased vasoconstriction.
authors.affiliation: Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Osmond
authors.forename: Laura V
authors.initials: LV
authors.lastname: Gonzalez Bosc
authors.forename: Benjimen R
authors.initials: BR
authors.lastname: Walker
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Kanagy
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010726:Phosphodiesterase Inhibitors; D014662:Vasoconstrictor Agents; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases
keywords: Ca2+ oscillations; endothelin-1; intermittent hypoxia