Caveolin-1 abolishment attenuates the myogenic response in murine cerebral arteries

Adebowale Adebiyi, Guiling Zhao, Sergey Y. Cheranov, Abu Ahmed, Jonathan Jaggar

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Intravascular pressure-induced vasoconstriction (the "myogenic response") is intrinsic to smooth muscle cells, but mechanisms that underlie this response are unresolved. Here we investigated the physiological function of arterial smooth muscle cell caveolae in mediating the myogenic response. Since caveolin-1 (cav-1) ablation abolishes caveolae formation in arterial smooth muscle cells, myogenic mechanisms were compared in cerebral arteries from control (cav-1+/+) and cav-1-deficient (cav-1 -/-) mice. At low intravascular pressure (10 mmHg), wall membrane potential, intracellular calcium concentration ([Ca2+]i), and myogenic tone were similar in cav-1+/+ and cav-1-/- arteries. In contrast, pressure elevations to between 30 and 70 mmHg induced a smaller depolarization, [Ca2+]i elevation, and myogenic response in cav-1-/- arteries. Depolarization induced by 60 mM K + also produced an attenuated [Ca2+]i elevation and constriction in cav-1-/- arteries, whereas extracellular Ca 2+ removal and diltiazem, an L-type Ca2+ channel blocker, similarly dilated cav-1+/+ and cav-1-/- arteries. Nω-nitro-L-arginine, an nitric oxide synthase inhibitor, did not restore myogenic tone in cav-1-/- arteries. Iberiotoxin, a selective Ca 2+-activated K+ (KCa) channel blocker, induced a similar depolarization and constriction in pressurized cav-1+/+ and cav-1-/- arteries. Since pressurized cav-1-/- arteries are more hyperpolarized and this effect would reduce KCa current, these data suggest that cav-1 ablation leads to functional KCa channel activation, an effect that should contribute to the attenuated myogenic constriction. In summary, data indicate that cav-1 ablation reduces pressure-induced depolarization and depolarization-induced Ca2+ influx, and these effects combine to produce a diminished arterial wall [Ca 2+]i elevation and constriction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Caveolin 1
Cerebral Arteries
Arteries
Constriction
Smooth Muscle Myocytes
Pressure
Caveolae
Diltiazem
Vasoconstriction

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Caveolin-1 abolishment attenuates the myogenic response in murine cerebral arteries. / Adebiyi, Adebowale; Zhao, Guiling; Cheranov, Sergey Y.; Ahmed, Abu; Jaggar, Jonathan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 3, 01.03.2007.

Research output: Contribution to journalArticle

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abstract = "Intravascular pressure-induced vasoconstriction (the {"}myogenic response{"}) is intrinsic to smooth muscle cells, but mechanisms that underlie this response are unresolved. Here we investigated the physiological function of arterial smooth muscle cell caveolae in mediating the myogenic response. Since caveolin-1 (cav-1) ablation abolishes caveolae formation in arterial smooth muscle cells, myogenic mechanisms were compared in cerebral arteries from control (cav-1+/+) and cav-1-deficient (cav-1 -/-) mice. At low intravascular pressure (10 mmHg), wall membrane potential, intracellular calcium concentration ([Ca2+]i), and myogenic tone were similar in cav-1+/+ and cav-1-/- arteries. In contrast, pressure elevations to between 30 and 70 mmHg induced a smaller depolarization, [Ca2+]i elevation, and myogenic response in cav-1-/- arteries. Depolarization induced by 60 mM K + also produced an attenuated [Ca2+]i elevation and constriction in cav-1-/- arteries, whereas extracellular Ca 2+ removal and diltiazem, an L-type Ca2+ channel blocker, similarly dilated cav-1+/+ and cav-1-/- arteries. Nω-nitro-L-arginine, an nitric oxide synthase inhibitor, did not restore myogenic tone in cav-1-/- arteries. Iberiotoxin, a selective Ca 2+-activated K+ (KCa) channel blocker, induced a similar depolarization and constriction in pressurized cav-1+/+ and cav-1-/- arteries. Since pressurized cav-1-/- arteries are more hyperpolarized and this effect would reduce KCa current, these data suggest that cav-1 ablation leads to functional KCa channel activation, an effect that should contribute to the attenuated myogenic constriction. In summary, data indicate that cav-1 ablation reduces pressure-induced depolarization and depolarization-induced Ca2+ influx, and these effects combine to produce a diminished arterial wall [Ca 2+]i elevation and constriction.",
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