Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings

Uydeş-Doğan, B. Sönmez; Topal, Gökçe; Takır, Selçuk; İlkay, F.; Kaleli, Deniz; Özdemir, Osman

doi:10.1016/j.lfs.2004.11.002

Cited by 23 publications

(16 citation statements)

References 34 publications

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“…Acute application of HMG-CoA reductase inhibitors (pravastatin, atorvastatin and cerivastatin) elicited an endothelium-dependent relaxation of pre-constricted rat isolated aorta, and cerivastatin-induced relaxation was attenuated by glibenclamide and ouabain [13]. Activation of cardiac K ATP channels by statins has been reported [14], [35], [36].…”

Section: Discussionmentioning

confidence: 98%

“…Porcine left anterior descending coronary artery myocytes and human left internal mammary artery myocytes were dissociated using collagenase and protease, as reported [3], [13] for conventional whole-cell patch-clamp electrophysiology experiments.…”

Section: Methodsmentioning

confidence: 99%

“…In addition to Ca 2+ channels and BK Ca channels, ATP-sensitive K + (K ATP ) channels are abundant in vascular tissues and K ATP channels are also important in regulating the vascular tone [12]. In rat isolated aorta, cerivastatin-induced a glibenclamide (a K ATP channel blocker)-sensitive aortic relaxation [13] and pravastatin reduced myocardial infact size through opening of mitochondrial K ATP channels in rabbit [14]. However, a recent study reported that simvastatin, but not pravastatin, inhibited pinacidil (a K ATP channel opener)-induced relaxation of pig’s isolated coronary arteries suggesting that different statins have differential effects on K ATP channels of different cells/tissues [40].…”

Section: Introductionmentioning

confidence: 99%

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Acute Simvastatin Inhibits KATP Channels of Porcine Coronary Artery Myocytes

Seto

Poon

et al. 2013

PLoS ONE

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BackgroundStatins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.MethodsPig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca2+]i, [ATP]i and [glucose]o uptake measurements.ResultsThe cromakalim (10 nM to 10 µM)- and pinacidil (10 nM to 10 µM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 µM). Simvastatin (1, 3 and 10 µM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 µM)- and pinacidil (10 µM)-mediated opening of whole-cell KATP channels of arterial myocytes. Simvastatin (10 µM) and AICAR (1 mM) elicited a time-dependent, compound C (1 µM)-sensitive [3H]-2-deoxy-glucose uptake and an increase in [ATP]i levels. A time (2–30 min)- and concentration (0.1–10 µM)-dependent increase by simvastatin of p-AMPKα-Thr172 and p-PP2A-Tyr307 expression was observed. The enhanced p-AMPKα-Thr172 expression was inhibited by compound C, ryanodine (100 µM) and KN93 (10 µM). Simvastatin-induced p-PP2A-Tyr307 expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 µM), and in [glucose]o-free or [Na+]o-free conditions.ConclusionsSimvastatin causes ryanodine-sensitive Ca2+ release which is important for AMPKα-Thr172 phosphorylation via Ca2+/CaMK II. AMPKα-Thr172 phosphorylation causes [glucose]o uptake (and an [ATP]i increase), closure of KATP channels, and phosphorylation of AMPKα-Thr172 and PP2A-Tyr307 resulted. Phosphorylation of PP2A-Tyr307 occurs at a site downstream of AMPKα-Thr172 phosphorylation.

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Section: Discussionmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute Simvastatin Inhibits KATP Channels of Porcine Coronary Artery Myocytes

Seto

Poon

et al. 2013

PLoS ONE

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“…The involvement of NO and K + channels in the vasorelaxant effect produced by rosuvastatin in aortic rings from rats with a CAF diet was investigated because it was reported that stimulation of NOS and the opening of Ca +2 ‐dependent K + channels are involved in those vasorelaxations to rosuvastatin and methyl ester of rosuvastatin on phenylephrine‐precontracted aortic rings of rats with standard diet . These findings about the involvement of NO and K + channels in the vasorelaxations produced by rosuvastatin on aortic rings of rat with CAF diet are in line with previous reports in which statins produced vasorelaxation and stimulation of NO and K + channels; they also corroborate several reports that suggest that NO and K + channels play an important role in the modulation of vascular tone …”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria‐style diet

López-Canales

Lozano-Cuenca

López-Canales

et al. 2015

Clin Exp Pharma Physio

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The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a semi-solid, cafeteria-style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine-precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10−9–10−5-mol/L rosuvastatin produced lower concentration-dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10−5-mol/L NG-nitro-l-arginine methyl ester, 10−2-mol/L tetraethylammonium, 10−3-mol/L 4-aminopyridine, 10−7-mol/L apamin plus 10−7-mol/L charybdotoxin, 10−5-mol/L indomethacin, or 10−5-mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine-precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca2+-activated and voltage-activated K+ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect.

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“…Lipid-modulating drugs statins (HMG-CoA reductase inhibitors) are a milestone to lower cholesterol levels in blood and become one of the most powerful pharmacological strategies in the treatment of cardiovascular diseases [16]. Statins could relax vascular tone importantly by endothelium-dependent pathway [17]. It exerts cholesterol-independent vasoprotective effects by upregulating endothelial nitric oxide synthase and decreasing superoxide production [18].…”

Section: Discussionmentioning

confidence: 99%

Daming capsule restores endothelial dysfunction induced by high-fat diet

Zhang

Niu

Wang

et al. 2012

BMC Complement Altern Med

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BackgroundDaming capsule (DMC), a traditional Chinese formula, has a lipid-modulating action with reduced adverse side effects as compared with other lipid lowering compounds. Since endothelial dysfunction often accompanies the hyperlipidemic state, we hypothesize that DMC might restore endothelial dysfunction produced by a high-fat (HF) diet. Importantly, we also investigate possible mechanisms involved in mediating the effects of DMC on vascular reactivity.MethodsRats were divided into four groups: control, HF diet, HF mixed DMC diet, HF mixed atorvastatin (ATV) diet. After 30 days, the thoracic cavity was exposed to remove the thoracic aorta for (i) histological examination; (ii) measurement of endothelial nitric oxide synthase (eNOS) by western blot; and (iii) tension study of thoracic aortic ring.ResultsHF diet induced significant attenuation in the contraction and relaxation of rat aortic rings. Treatment with DMC significantly improved the relaxation of the aortic rings as compared with those from HF rats (P < 0.05), which was abolished by a nonspecific NOS inhibitor L-NAME. Moreover DMC significantly restored the decrease in eNOS expression induced by HF diet. Similar results were found in histopathologic changes. DMC failed to restore the loss of vasocontraction of aorta explained by an impairment of ATP-sensitive K+ channels (KATP) on the structure and/or function. DMC exerted the same protective effect as ATV, a positive control drug, on vascular injury produced by HF diet.ConclusionDMC partially protects the aorta from HF-induced endothelial dysfunction via upregulation of the expression of eNOS.

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Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings

Cited by 23 publications

References 34 publications

Acute Simvastatin Inhibits KATP Channels of Porcine Coronary Artery Myocytes

Acute Simvastatin Inhibits KATP Channels of Porcine Coronary Artery Myocytes

Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria‐style diet

Daming capsule restores endothelial dysfunction induced by high-fat diet

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