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Lovastatin Induces Relaxation and Inhibits L-Type Ca2+ Current in the Rat Basilar Artery.

Bergdahl, Andreas LU ; Persson, Erik; Hellstrand, Per LU and Swärd, Karl LU (2003) In Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00 93(3). p.128-134
Abstract
Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 μmol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was... (More)
Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 μmol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was not reversed by mevalonate, suggesting that it was not related to cholesterol or isoprenoid metabolism. Relaxation was associated with a reduction of the intracellular Ca2+ concentration measured with Fura 2 and with a reduced Mn2+ quench rate, suggesting a direct effect on ion channels in the smooth muscle cell membrane. Current measurements in isolated and voltage clamped basilar artery muscle cells demonstrated that both lovastatin and lovastatin acid inhibit L-type Ca2+ current. We propose that lipophilicity is an important factor behind the effects of statins on vascular tone and that Ca2+ current inhibition is the likely mechanism of action. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00
volume
93
issue
3
pages
128 - 134
publisher
Wiley-Blackwell
external identifiers
  • wos:000185481500004
  • pmid:12969437
  • scopus:0043237774
ISSN
1600-0773
DOI
10.1034/j.1600-0773.2003.930304.x
language
English
LU publication?
yes
id
1ab11fd4-15ab-4d56-943b-4d69d022174d (old id 117829)
date added to LUP
2007-07-10 11:51:37
date last changed
2018-01-07 05:47:46
@article{1ab11fd4-15ab-4d56-943b-4d69d022174d,
  abstract     = {Statins inhibit cholesterol biosynthesis and protect against ischaemic stroke. It has become increasingly apparent that the beneficial effects of statin therapy may extend beyond lowering of serum cholesterol. The present study was done to explore possible pleiotropic statin effects at the level of the cerebral vascular smooth muscle. Lovastatin, lovastatin acid, simvastatin and pravastatin, were added to segments of the rat basilar artery and effects on contraction and Ca2+ handling were examined. Pravastatin had no effect on contraction. Simvastatin, lovastatin, and, to a lesser degree, lovastatin acid, caused relaxation (IC50=0.8, 1.9 and 22 μmol/l) of both intact and denuded arteries precontracted with 5-HT or high-K+. This effect was not reversed by mevalonate, suggesting that it was not related to cholesterol or isoprenoid metabolism. Relaxation was associated with a reduction of the intracellular Ca2+ concentration measured with Fura 2 and with a reduced Mn2+ quench rate, suggesting a direct effect on ion channels in the smooth muscle cell membrane. Current measurements in isolated and voltage clamped basilar artery muscle cells demonstrated that both lovastatin and lovastatin acid inhibit L-type Ca2+ current. We propose that lipophilicity is an important factor behind the effects of statins on vascular tone and that Ca2+ current inhibition is the likely mechanism of action.},
  author       = {Bergdahl, Andreas and Persson, Erik and Hellstrand, Per and Swärd, Karl},
  issn         = {1600-0773},
  language     = {eng},
  number       = {3},
  pages        = {128--134},
  publisher    = {Wiley-Blackwell},
  series       = {Pharmacology and Toxicology1987-01-01+01:002004-01-01+01:00},
  title        = {Lovastatin Induces Relaxation and Inhibits L-Type Ca2+ Current in the Rat Basilar Artery.},
  url          = {http://dx.doi.org/10.1034/j.1600-0773.2003.930304.x},
  volume       = {93},
  year         = {2003},
}