Abstract
This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca 2+ o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl- cotransport (NKCC) inhibitor, decreased Cl- i content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o=36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cl- i-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further.
| Original language | English |
|---|---|
| Pages (from-to) | 42-55 |
| Number of pages | 14 |
| Journal | Pflugers Archiv European Journal of Physiology |
| Volume | 449 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Oct 2004 |
| Externally published | Yes |
Fingerprint
Keywords
- Ca channels
- Cell volume
- Contraction
- Intracellular Cl
- Na,K,2Cl cotransport
- Smooth muscle
ASJC Scopus subject areas
- Physiology
Cite this
Cell-volume-dependent vascular smooth muscle contraction : Role of Na +, K+, 2Cl- cotransport, intracellular Cl - and L-type Ca2+ channels. / Anfinogenova, Yana J.; Baskakov, Mikhail B.; Kovalev, Igor V.; Kilin, Alexander A.; Dulin, Nickolai O.; Orlov, Sergei N.
In: Pflugers Archiv European Journal of Physiology, Vol. 449, No. 1, 10.2004, p. 42-55.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Cell-volume-dependent vascular smooth muscle contraction
T2 - Role of Na +, K+, 2Cl- cotransport, intracellular Cl - and L-type Ca2+ channels
AU - Anfinogenova, Yana J.
AU - Baskakov, Mikhail B.
AU - Kovalev, Igor V.
AU - Kilin, Alexander A.
AU - Dulin, Nickolai O.
AU - Orlov, Sergei N.
PY - 2004/10
Y1 - 2004/10
N2 - This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca 2+ o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl- cotransport (NKCC) inhibitor, decreased Cl- i content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o=36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cl- i-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further.
AB - This study elucidates the role of cell volume in contractions of endothelium-denuded vascular smooth muscle rings (VSMR) from the rat aorta. We observed that hyposmotic swelling as well as hyper- and isosmotic shrinkage led to VSMR contractions. Swelling-induced contractions were accompanied by activation of Ca2+ influx and were abolished by nifedipine and verapamil. In contrast, contractions of shrunken cells were insensitive to the presence of L-type channel inhibitors and occurred in the absence of Ca 2+ o. Thirty minutes preincubation with bumetanide, a potent Na+,K+,Cl- cotransport (NKCC) inhibitor, decreased Cl- i content, nifedipine-sensitive 45Ca uptake and contractions triggered by modest depolarization ([K+]o=36 mM). Elevation of [K+]o to 66 mM completely abolished the effect of bumetanide on these parameters. Bumetanide almost completely abrogated phenylephrine-induced contraction, partially suppressed contractions triggered by hyperosmotic shrinkage, but potentiated contractions of isosmotically shrunken VSMR. Our results suggest that bumetanide suppresses contraction of modestly depolarized cells via NKCC inhibition and Cl- i-mediated membrane hyperpolarization, whereas augmented contraction of isosmotically shrunken VSMR by bumetanide is a consequence of suppression of NKCC-mediated regulatory volume increase. The mechanism of bumetanide inhibition of contraction of phenylephrine-treated and hyperosmotically shrunken VSMR should be examined further.
KW - Ca channels
KW - Cell volume
KW - Contraction
KW - Intracellular Cl
KW - Na,K,2Cl cotransport
KW - Smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=8644237315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8644237315&partnerID=8YFLogxK
U2 - 10.1007/s00424-004-1316-z
DO - 10.1007/s00424-004-1316-z
M3 - Article
C2 - 15293051
AN - SCOPUS:8644237315
VL - 449
SP - 42
EP - 55
JO - Pflugers Archiv European Journal of Physiology
JF - Pflugers Archiv European Journal of Physiology
SN - 0031-6768
IS - 1
ER -