Regulation of RhoA/ROCK and sustained arterial contraction by low cytosolic Ca2+ levels during prolonged depolarization of arterial smooth muscle.
Vascul Pharmacol
; 93-95: 33-41, 2017 08.
Article
em En
| MEDLINE
| ID: mdl-28526517
ABSTRACT
The role of L-type Ca2+ channels (LTCCs) and RhoA/Rho kinase (ROCK) on depolarization-induced sustained arterial contraction lasting several minutes is already known. However, in vivo, vascular smooth muscle cells can be depolarized for longer periods, inducing substantial inactivation of LTCCs and markedly reducing Ca2+ influx into the myocytes. We have examined, in femoral arterial rings, the role of LTCCs and RhoA/ROCK during long-lasting depolarization. Our results reveal a new vasoreactive response after 20-30min of depolarization in 2.5mM external Ca2+ that has not been identified previously with shorter stimuli. Prolonged depolarization-induced arterial contraction was permanently abolished when arterial rings were treated with 100nM external Ca2+ or 20nM nifedipine. However, when Ca2+ influx was restricted, applying ~7µM external Ca2+ solution or 3nM nifedipine, vasorelaxation was transient, and isometric force slowly increased after 30min and maintained its level until the end of the stimulus. Under these conditions, arterial contraction showed the same temporal course of RhoA activity and was sensitive to fasudil, nifedipine and cyclopiazonic acid. Ca2+-response curve in ß-escin permeabilized arteries was also sensitive to ROCK inhibitors. Thus, although long-lasting depolarization inactivates LTCCs, the reduced Ca2+ entry can induce a detectable arterial contraction via RhoA/ROCK activation.
Palavras-chave
Acetylcholine chloride (PubChem CID: 6060); Arterial vasospasm; EGTA (PubChem CID: 6207); Endothelin-I (PubChem CID: 16212950); Fasudil dihydrochloride (PubChem CID: 16219471); L-type Ca(2+) channels; Long-lasting depolarization; Nifedipine (PubChem CID: 4485); RhoA/Rho-associated kinase; ß-escin (PubChem CID: 16211024)
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasoconstrição
/
Cálcio
/
Sinalização do Cálcio
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Proteínas rho de Ligação ao GTP
/
Canais de Cálcio Tipo T
/
Quinases Associadas a rho
/
Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article