PDF herunterladen
Arzneimittelforschung 2011; 61(7): 386-392
DOI: 10.1055/s-0031-1296216
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Effects of calcium antagonists and agonists on isolated human v. saphena magna used for coronary artery bypass grafting and guinea pig’s papillary muscle

Vida Garaliene
1   Institute of Cardiology at Medical Academy of Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Vygantas Barsys
1   Institute of Cardiology at Medical Academy of Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Povilas Jakuška
2   Department of Cardiothoracic and Vascular Surgery at Lithuanian University of Health Sciences, Kaunas, Lithuania
,
Aivars Krauze
3   Latvian Institute of Organic Synthesis, Riga, Latvia
,
Gunar Duburs
3   Latvian Institute of Organic Synthesis, Riga, Latvia
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
27. November 2011 (online)

    Lizenzen und Reprints

Abstract

Background:

The goal of this study was to investigate the movement of contraction-relaxation effects on isolated human blood vessel samples by the actions of amlodipine (CAS 88150-42-9), cerebrocrast (CAS 118790-71-9), diltiazem (CAS 42399-41-7), and a benzimidazole derivative. Additionally, their effects on isometric contraction force and the duration of the action potential (AP) were measured.

Methods:

The experiments were carried out on isolated human v. saphena magna samples and papillary muscles of adult guinea pigs. Isometric contraction and the AP were recorded using a force transducer and standard microelectrode technique.

Results:

Phenylephrine (10−4 M) caused contractions of vein rings to 928 ± 76.5 mg. All the tested agents at a concentration of 10−7–10−4 M significantly relaxed the smooth muscle in a dose-dependent manner. The weakest response was shown by amlodipine. Pre-treatment with 50 >M of amlodipine, diltiazem and benzimidazole for 30 min significantly increased the magnitude of the contraction induced by phenylephrine in concentration-dependent (10−6–10−4) fashion but only in the benzimidazole group versus other tested agents and the control. The benzimidazole derivative caused augmentation of isometric contraction of the papillary muscles and negligible lengthening of AP duration; the other agents tested showed opposite effects.

Conclusion:

These results show that agents possessing positive or negative inotropic action significantly relaxed the isolated vein samples precontracted with phenylephrine. These responses point to a different mechanism of action underlying both calcium antagonist and agonist effects even though their action ultimately resulted in vasodilatation.

Key words

1-Acetyl-5,6-dimethoxy-2-methylthiobenzimidazole - Amlodipine - Cerebrocrast - Diltiazem - Guinea pig papillary muscles - Human v. saphena magna
 

  • References

  • 1 Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation 2005; 111: 363-8
    CrossrefPubMedGoogle Scholar
  • 2 Garaliene V. [The main determinants of endothelial dysfunction]. Mediana (Kaunas) 2006; 42: 362-9 Lithuanian. Abstract in English.
    PubMedGoogle Scholar
  • 3 Feletou M, Vanhoutte PM. Endothelial dysfunction: a mul-tifaceted disorder. Am J Physiol Heart Circ Physiol 2006; 291: H985-1002
    CrossrefPubMedGoogle Scholar
  • 4 Zhang XP, Hintze TH. cAMP signal transduction induces eNOS activation by promoting PKB phosphorylation. Am J Physiol Heart Circ Physiol 2006; 290: H2376-84
    CrossrefPubMedGoogle Scholar
  • 5 Matsumoto T, Kobayashi T, Kamata K. Phosphodiesterase in the vascular system. J Smooth Muscle Res 2003; 39 (4) 67-86
    CrossrefPubMedGoogle Scholar
  • 6 Thompson PE, Manganiello V, Degerman E. Re-discovering PDE3 inhibitors – new opportunities for a long neglected target. Curr Top Med Chem 2007; 7: 421-36
    CrossrefPubMedGoogle Scholar
  • 7 Kwak YL, Oh YJ, Kim SH, Shin HK, Kim JY, Hong YW. Efficacy of pre-emptive milrinone in off-pump coronary artery bypass surgery: comparison between patients with a low and normal pre-graft cardiac index. Eur J Cardiothorac Surg 2004; 26: 687-93
    CrossrefPubMedGoogle Scholar
  • 8 Klusa V. Cerebrocrast, neuroprotectant, cognition enhancer. Drugs of the Future 1995; 20: 135-8
    PubMedGoogle Scholar
  • 9 Klusa V. Cerebrocrast, a cognition enhancer and neuroprotectant: focus on mitochondrial functions. Auton Autacoid Pharmacol 2006; 26 (1) 60-2
    PubMedGoogle Scholar
  • 10 Briede J, Stivrina M, Vigante B, Stoldere D, Duburs G. Acute effect of antidiabetic 1,4-dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in isolated, perfused normal rat heart. Cell Biochem Funct 2008; 26: 238-45
    CrossrefPubMedGoogle Scholar
  • 11 Vicente JAF, Duburs G, Klusa V, Briede J, Klimaviciusa L, Zharkovsky A et al. Cerebrocrast as a neuroprotective, antidiabetic and mitochondrial bioenergetic effector: a putative mechanism of action. In: Moreno AJM, Oliveira PJ, Palmeira CM. eds. Mitochondrial Pharmacology and Toxicology. Transworld Reseach Network, Kerala 2006: 185-9
    Google Scholar
  • 12 Brukshtus AB, Garalene VN, Sirvidite AP, Daukshas VK. Synthesis and cardiotonic activity of 1-acyl-2-methylthio-5,6-dimethoxybenzimidazole derivatives. Pharm Chem J 1995; 29 (5) 328-9
    CrossrefPubMedGoogle Scholar
  • 13 Garaliene V, Labanauskas L, Brukštus A, Daukšas V. Synthesis and positive inotropic effects of 1-acyl-5,6-dieth-oxy-2-methylthiobenzimidazoles. Arzneimittelforschung 1998; 48: 1137-42
    PubMedGoogle Scholar
  • 14 Garaliene V, Labanauskas L, Brukštus A. Effect of 1-Acyl-5,6-dialkoxy-2-alkylthiobenzo[d]imidazoles on the action potential duration and isometric contraction in guinea pig atrium activated by carbachol and guinea pig heart papillary muscles. Arzneimittelforschung 2006; 56: 282-7
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 15 Early S. Nelson MT. Central role of Ca2+-dependent regulation of vascular tone in vivo. J Appl Physiol 2006; 101: 10-1
    PubMedGoogle Scholar
  • 16 Raggi P, Shaw AM. Epidemiological guidance with coronary artery calcium scoring. Curr Cardiol Rep 2008; 10: 60-6
    CrossrefPubMedGoogle Scholar
  • 17 Al-Qaisi M, Kharbanda RK, Mittal TK, Donald AE. Measurement of endothelial function and its clinical utility for cardiovascular risk. Vascular Health Risk Management 2008; 4: 647-52
    PubMedGoogle Scholar
  • 18 Manabe S, Sunamori M. Radial artery graft for coronary artery bypass surgery: biological characteristics and clinical outcome. J Card Surg 2006; 21: 102-14
    CrossrefPubMedGoogle Scholar
  • 19 He GW, Fan Li, Furnary A, Yang Q. A new antispastic solution for arterial grafting: nicardipine and nitroglycerin cocktail in preparation of internal thoracic and radial arteries for coronary surgery. J Thorac Cardiovasc Surg 2008; 136: 673-80
    CrossrefPubMedGoogle Scholar
  • 20 Attaran S, John L, El-Gamel A. Clinical and potential use of pharmacological agents to reduce radial artery spasm in coronary artery surgery. Ann Thorac Surg 2008; 85: 1483-9
    CrossrefPubMedGoogle Scholar
  • 21 Steffen HM. Amlodipine – third generation dihydropyri-dine calcium antagonist. J Clin Basic Cardiol 1999; 2 (1) 45-52
    PubMedGoogle Scholar
  • 22 Mason RP, Marche P, Hintze TH. Novel vascular biology of third-generation L-type calcium channel antagonists. Ancillary actions of amlodipine. Arteriscler Thromb Vasc Biol 2003; 23: 2155-63
    PubMedGoogle Scholar
  • 23 Shapira OM, Xu A, Vita JA, Aldea GS, Shah N, Shemin RJ et al. Nitroglycerin is superior to diltiazem as a coronary bypass conduit vasodilator. J Thorac Cardiovasc Surg 1999; 117: 906-11
    CrossrefPubMedGoogle Scholar
  • 24 Ruschithka FT, Noll G, Lüscher TF. Calcium antagonists and endothelial function. J Clin Basic Cardiol 1999; (2) 175-80
    PubMedGoogle Scholar
  • 25 Duburs G, Vigante B, Plotniece A, Krauze A, Sobolevs A, Briede J et al. Dihydropyridine derivatives as bioprotectors. Chemistry Today 2008; 26 (2) 68-70
    PubMedGoogle Scholar
  • 26 Zhang X, Hintze T. Amlodipine releases nitric oxide from canine coronary microvessels. An unexpected mechanism of action of a calcium channel blocking agent. Circulation 1998; 97: 576-80
    CrossrefPubMedGoogle Scholar
  • 27 Zhang XP, Loke KE, Mital S, Chahwala S, Hintze TH. Paradoxical release of nitric oxide by an L-type calcium channel antagonist, the R+ enantiomer of amlodipine. J Cardiovasc Pharmacol 2002; 39: 208-14
    CrossrefPubMedGoogle Scholar
  • 28 Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH. K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 1998; 396: 269-72
    CrossrefPubMedGoogle Scholar
  • 29 Stankevicius E, Hughes AD, Simonsen U. K+ channels and release of nitric oxide. Fund Clin Pharmacol 2008; 22 (2) 9
    PubMedGoogle Scholar
  • 30 Brekke JF, Jackon WF, Segal SS. Arteriolar smooth muscle Ca2+ dynamics during blood flow control in hamster cheek pouch. J Appl Physiol 2006; 101: 307-15
    CrossrefPubMedGoogle Scholar
  • 31 Kudej RK, Zhang XP, Ghalen B, Huang CH, Jackson JB, Kudej AB et al. Enhanced cAMP-induced nitric oxide-dependent coronary dilation during myocardial stunning in conscious pigs. Am J Physiol Heart Circ Physiol 2000; 279: H2967-74
    PubMedGoogle Scholar
  • 32 Levy JH, Bailey JM, Deeb GM. Intravenous milrinone in cardiac surgery. Ann Thorac Surgery 2002; 73: 325-30
    CrossrefPubMedGoogle Scholar
  • 33 Feletou M. Calcium-activated potassium channels and endothelial dysfunction: therapeutic options?. Br J Pharmacol 2009; 156: 545-62
    CrossrefPubMedGoogle Scholar
  • 34 Porter VA, Bonev AD, Knot HJ, Heppner TJ, Stevenson AS, Kleppisch T et al. Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides. Am J Physiol (Cell Physiol. 43) 1998; 274 (5 Pt 1) C1346-55
    PubMedGoogle Scholar
  • 35 Feng J, Liu Y, Clements RT, Sodha NR, Khabbaz K, Senthilnathan V et al. Calcium-activated potassium channels contribute to human coronary microvascular dysfunction after cardioplegic arrest. Circulation 2008; 118: S46-51
    CrossrefPubMedGoogle Scholar
  • 36 Zhang XP, Tada H, Wang Z, Hintze TH. cAMP signal transduction, a potential compensatory pathway for coronary endothelial NO production after heart failure. Arterioscler Thromb Vasc Biol 2002; 22: 1273-8
    CrossrefPubMedGoogle Scholar
  • 37 Bers DM. Calcium and cardiac rhythms. Physiological and pathophysiological. Circ Res 2002; 90: 14-7
    PubMedGoogle Scholar
  • 38 Ademuyiwa AS, Blatter AA, Blatter LA. Modulation of intracellular Ca2+ release and capacitative Ca2+ entry by CAMKII inhibitors in bovine vascular endothelial cells. Am J Physiol Cell Physiol 2005; 289: C1426-36
    CrossrefPubMedGoogle Scholar