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Cholesterol Depletion Impairs Vascular Reactivity to Endothelin-1 by Reducing Store-Operated Ca 2+ Entry Dependent on TRPC1
- Source :
- Circulation Research. 93:839-847
- Publication Year :
- 2003
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2003.
-
Abstract
- The reactivity of the vascular wall to endothelin-1 (ET-1) is influenced by cholesterol, which is of possible importance for the progression of atherosclerosis. To elucidate signaling steps affected, the cholesterol acceptor methyl-β-cyclodextrin (mβcd, 10 mmol/L) was used to manipulate membrane cholesterol and disrupt caveolae in intact rat arteries. In endothelium-denuded caudal artery, contractile responsiveness to 10 nmol/L ET-1 (mediated by the ET A receptor) was reduced by mβcd and increased by cholesterol. Neither ligand binding nor colocalization of ET A and caveolin-1 was affected by mβcd. Ca 2+ inflow via store-operated channels after depletion of intracellular Ca 2+ stores was reduced in mβcd-treated caudal arteries, as shown by Mn 2+ quench rate and intracellular [Ca 2+ ] response. Expression of TRPC1, 3, and 6 was detected by reverse transcriptase–polymerase chain reaction, and colocalization of TRPC1 with caveolin-1 was reduced by mβcd, as seen by immunofluorescence. Part of the contractile response to ET-1 was inhibited by Ni 2+ (0.5 mmol/L) and by a TRPC1 blocking antibody. In the basilar artery, exhibiting less store-operated channel activity than the caudal artery, ET-1–induced contractions were insensitive to the TRPC1 blocking antibody and to mβcd. Increased store-operated channel activity in basilar arteries after organ culture correlated with increased sensitivity of ET-1 contraction to mβcd. These results suggest that cholesterol influences vascular reactivity to ET-1 by affecting the caveolar localization of TRPC1.
- Subjects :
- Tail
medicine.medical_specialty
Physiology
Caveolin 1
Biology
Ligands
Binding, Competitive
Caveolins
Ion Channels
Rats, Sprague-Dawley
TRPC1
Culture Techniques
Internal medicine
medicine.artery
Caveolae
medicine
Basilar artery
Animals
Caudal artery
TRPC Cation Channels
Dose-Response Relationship, Drug
Endothelin-1
Colocalization
Arteries
Receptor, Endothelin A
Endothelin 1
Rats
Vasomotor System
Cholesterol
Endocrinology
medicine.anatomical_structure
Biochemistry
Basilar Artery
Calcium
Female
Calcium Channels
medicine.symptom
Cardiology and Cardiovascular Medicine
Endothelin receptor
Vasoconstriction
Subjects
Details
- ISSN :
- 15244571 and 00097330
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Circulation Research
- Accession number :
- edsair.doi.dedup.....70808b0f45f80da79750e3330cb98c05