Improvement of ischemic myocardial dysfunction by nisoldipine

Saida, Kooichi; Umeda, Masaomi; Itakura, Akemi

doi:10.1007/bf00877321

Cited by 6 publications

(3 citation statements)

References 18 publications

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“…28 Complementary evidence is provided by the inhibition of ischemic contracture, and attendant cardioprotection on reperfusion, by nisoldipine, an L-type Ca 2ϩ channel antagonist. 10 In any event, the increased production/release of ET-1 during ischemia or reperfusion, 12 possibly together with an increased availability of ET-1 binding sites through externalization triggered in these states, 29 clearly exerted proischemic effects in the present model that were attenuated by antagonists with high affinity for ET A receptors. It is inferred that the contracture-enhancing effect exerted by 100 pmol/L ET-1 was also mediated by ET A receptors.…”

Section: Effects Of Et-1 On Diastolic Pressure-volume Relationship (Imentioning

confidence: 74%

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Role of Endothelin-A Receptors in Ischemic Contracture and Reperfusion Injury

Brünner

Opie

1998

Circulation

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Section: Effects Of Et-1 On Diastolic Pressure-volume Relationship (Imentioning

confidence: 74%

“…Two primary cellular mechanisms have been proposed: (1) severe depletion of ATP with inability to sequester Ca 2ϩ and (2) a raised diastolic cytosolic Ca 2ϩ concentration. 9 Although Ca 2ϩ entry blockers of different classes may prevent ischemic contracture, 10 the pathophysiological mediators of Ca 2ϩ entry are not known.…”

mentioning

confidence: 99%

Role of Endothelin-A Receptors in Ischemic Contracture and Reperfusion Injury

Brünner

Opie

1998

Circulation

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“…The anti‐adrenergic effects of NO may decrease cytosolic Ca 2+ levels during ischaemia and prevent or decrease cytosolic Ca 2+ overload during reperfusion. In support, ischaemic contracture is inhibited by nisoldipine, a L ‐type Ca 2+ channel antagonist (Saida et al , 1994). In the present study nitroprusside stimulated the synthesis of cyclic GMP, which probably counteracted the pro‐ischaemic and energy‐expending actions of endogenous noradrenaline.…”

Section: Discussionmentioning

confidence: 99%

Effect of nitrovasodilators and inhibitors of nitric oxide synthase on ischaemic and reperfusion function of rat isolated hearts

Toit

McCarthy

Miyashiro

et al. 1998

British J Pharmacology

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1 The functional role of the nitric oxide (NO)/guanosine 3':5'-cyclic monophosphate (cyclic GMP) pathway in experimental myocardial ischaemia and reperfusion was studied in rat isolated hearts. 2 Rat isolated hearts were perfused at constant pressure with Krebs-Henseleit bu er for 25 min (baseline), then made ischaemic by reducing coronary¯ow to 0.2 ml min 71 for 25 or 40 min, and reperfused at constant pressure for 25 min. Drugs inhibiting or stimulating the NO/cyclic GMP pathway were infused during the ischaemic phase only. Ischaemic contracture, myocardial cyclic GMP and cyclic AMP levels during ischaemia, and recovery of reperfusion mechanical function were monitored. 3 At baseline, heart rate was 287+12 beats min 71 , coronary¯ow was 12.8+0.6 ml min 71 , left ventricular developed pressure (LVDevP) was 105+4 mmHg and left ventricular end-diastolic pressure 4.6+0.2 mmHg in vehicle-treated hearts (control; n=12). Baseline values were similar in all treatment groups (P40.05). 4 In normoxic perfused hearts, 1 mM N G -nitro-L-arginine (L-NOARG) signi®cantly reduced coronarȳ ow from 13.5+0.2 to 12.1+0.1 ml min 71 (10%) and LVDevP from 97+1 to 92+1 mmHg (5%; P50.05, n=5). 5 Ischaemic contracture was 46+2 mmHg, i.e. 44% of LVDevP in control hearts (n=12), una ected by low concentrations of nitroprusside (1 and 10 mM) but reduced to *30 mmHg (*25%) at higher concentrations (100 or 1000 mM; P50.05 vs control, n=6). Conversely, the NO synthase inhibitor L-NOARG reduced contracture at 1 mM to 26+3 mmHg (23%), but increased it to 63+4 mmHg (59%) at 1000 mM (n=6). Dobutamine (10 mM) exacerbated ischaemic contracture (81+3 mmHg; n=7) and the cyclic GMP analogue Sp-8-(4-p-chlorophenylthio)-3',5'-monophosphorothioate (Sp-8-pCPT-cGMPS; 10 mM) blocked this e ect (63+1 mmHg; P50.05 vs dobutamine alone, n=5). 6 At the end of reperfusion, LVDevP was 58+5 mmHg, i.e. 55% of pre-ischaemic value in control hearts, signi®cantly increased to *80% by high concentrations of nitroprusside (100 or 1000 mM) or L-NOARG at 1 mM, while a high concentration of L-NOARG (1000 mM) reduced LVDevP to *35% (P50.05 vs control; n=6). 7 Ischaemia increased tissue cyclic GMP levels 1.8 fold in control hearts (P50.05; n=12); nitroprusside at 1 mM had no sustained e ect, but increased cyclic GMP *6 fold at 1000 mM; L-NOARG (1 or 1000 mM) was without e ect (n=6). Nitroprusside (1 or 1000 mM) marginally increased cyclic AMP levels whereas NO synthase inhibitors had no e ect (n=6). 8 In conclusion, the cardioprotective e ect of NO donors, but not of low concentrations of NO synthase inhibitors may be due to their ability to elevate cyclic GMP levels. Because myocardial cyclic GMP levels were not a ected by low concentrations of NO synthase inhibitors, their bene®cial e ect on ischaemic and reperfusion function is probably not accompanied by reduced formation of NO and peroxynitrite in this model.

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Effects of salvianolic acid B on L-type calcium channels and myocardial contractility in isolated rat ventricular myocytes and hERG K+ channels expressed in HEK293 cells

Song

Han

Xue

et al. 2017

Naunyn-Schmiedeberg's Arch Pharmacol

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Salvianolic acid B (Sal B), one of the chief water-soluble constituents in Radix Salviae Milthiorrhizae, has often been reported to possess considerable cardiovascular regulatory effects. However, the underlying biochemical and cellular mechanisms of its cardioprotection remain unclear. This study was designed to evaluate the role of Sal B regulation in L-type Ca channel currents (I) and cell contractility in rat cardiomyocytes and hERG K channels expressed in HEK293 cells with the patch-clamp and Ca imaging techniques to clarify its underlying cardioprotective mechanisms. Exposure to Sal B blocked I with IC of 2.07 × 10 M, shifted the curves of current and voltage upwards, shifted the curves of activation and inactivation to the left, and significantly inhibited the amplitude of the cell shortening, but the regulatory effects of Sal B on the expressed rapidly activating delayed rectifier potassium current (I) did not reach a significant level. These results indicate that the cardioprotective mechanisms of Sal B may be related to the attenuation of calcium overload by directly inhibiting I and consequently decreasing myocardial contractility without causing drug-induced long QT syndrome (LQTS).

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Improvement of ischemic myocardial dysfunction by nisoldipine

Cited by 6 publications

References 18 publications

Role of Endothelin-A Receptors in Ischemic Contracture and Reperfusion Injury

Role of Endothelin-A Receptors in Ischemic Contracture and Reperfusion Injury

Effect of nitrovasodilators and inhibitors of nitric oxide synthase on ischaemic and reperfusion function of rat isolated hearts

Effects of salvianolic acid B on L-type calcium channels and myocardial contractility in isolated rat ventricular myocytes and hERG K+ channels expressed in HEK293 cells

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