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Vascular relaxing mechanism of denopamine in isolated canine coronary, femoral, mesenteric, and renal arteries

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Summary

We investigated the mechanism of vascular relaxation produced by denopamine (deno), an oral positive inotropic agent that has selective β1-adrenergic action. Deno concentration-dependently (0.1 µM–30 µM) relaxed ring segments of canine femoral, mesenteric, and renal arteries which were partially precontracted with 1 µm phenylephrine or norepinephrine, but did not relax those precontracted with 5 µM prostaglandin F or 40 mM K+. The relaxation was not significantly inhibited by pretreatment with 10 µM propranolol or metoprolol. Deno produced a parallel rightward shift in concentration-response curves to phenylephrine in femoral and renal arteries. The Schild plot yielded linear regressions of slopes of 1.301 ± 0.106 and 0.823 ± 0.122, respectively, which were not significantly different from unity. The pA2 values of Deno against phenylephrine in femoral and renal arteries were 5.41 ± 0.03 and 5.76 ± 0.06, respectively.

On the other hand, Deno concentration-dependently (10 nM–10 µM) relaxed ring segments of canine coronary arteries which were partially precontracted with 5 µM prostaglandin F. The relaxation was significantly inhibited by pretreatment with 10 µM metoprolol.

In conclusion, vascular smooth muscle relaxation by Deno was mediated through β1-adrenergic action in canine coronary arteries and through the blocking effect of α-adrenoceptors in canine femoral, mesenteric, and renal arteries.

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References

  1. Kino M, Hirota Y, Yamamoto S, Sawada K, Moriguchi M, Kotaka M, Kubo S, Kawamura K (1983) Cardiovascular effects of a newly synthesized cardiotonic agent (TA-064) on normal and diseased hearts. Am J Cardiol 51:802–810

    Google Scholar 

  2. Takarada A, Yokota Y, Fukuzaki H (1987) Effect of a new cardiotonic agent, “TA-064”, in patients with dilated cardiomyopathy: Relationship between cardiac effect of TA-064 and severity of myocardial lesion, Jpn Circ J 51:251–258

    Google Scholar 

  3. Nagao T, Ikeo T, Murata S, Sato M, Nakajima H (1984) Cardiovascular effects of a new positive inotropic agent, (−)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl) amino] ethanol (TA-064) in the anesthetized dog and isolated guinea pig heart. Jpn J Pharmacol 35:415–423

    Google Scholar 

  4. Ikeo T, Nagao T, Suzuki T, Yabana H, Nakajima H (1985) Cardiovascular effects and plasma levels of denopamine (TA-064), a new positive inotropic agent, in chronically instrumented dogs. Jpn J Pharmacol 39:191–199

    Google Scholar 

  5. Ikeo T, Nagao T, Murata S, Yabana H, Sato M, Nakajima H (1986) Cardiovascular effects of the new positive inotropic agent denopamine, with special reference to species difference and the effect on failing heart. Arzneimittelforsch 36(2):1063–1068

    Google Scholar 

  6. Naito K, Nagao T, Otsuka M, Harigaya S, Nakajima H (1985) Studies on the affinity and selectivity of denopamine (TA-064), a new cardiotonic agent, for β-adrenergic receptors. Jpn J Pharmacol 38:235–241

    Google Scholar 

  7. Bing RJ, Sasaki Y, Burger W, Chemnitius JM (1984) Cardiac inotropic response of a new β1-agonist (TA-064) with low sarcolemmal adenylate cyclase activation. Curr Ther Res 36:1127–1144

    Google Scholar 

  8. Inamasu M, Totsuka T, Ikeo T, Nagao T, Takeyama S (1987) Beta1-adrenergic selectivity of the new cardiotonic agent, denopamine, in its stimulating effects on adenylate cyclase. Biochem Pharmacol 36:1947–1954

    Google Scholar 

  9. Ozaki N, Bito K, Kinoshita M, Kawakita S (1983) Effects of a cardiotonic agent, TA-064, on isolated canine cerebral, coronary, femoral, mesenteric, and renal arteries. J Cardiovasc Pharmacol 5:818–821

    Google Scholar 

  10. Aikawa J, Moroi M, Namiki A, Nakamura M, Yabuki S, Machii K, Akatsuka N (1990) A difference in vascular smooth muscle relaxation of denopamine and isoproterenol. J Jpn Coll Angiol 30:1137–1142

    Google Scholar 

  11. Aikawa J, Koike K, Takayanagi I (1991) Vascular smooth muscle relaxation by α1-adrenoceptor blocking action of denopamine in isolated rabbit aorta. J Cardiovasc Pharmacol 17:440–444

    Google Scholar 

  12. Tallarida RJ, Kowan A, Adler MW (1979) pA2 and receptor differentiation: a statistical analysis of competitive antagonism. Life Sci 25:637–654

    Google Scholar 

  13. Arunlakshana G, Schild HO (1959) Some quantitative uses of drug antagonists. Br J Pharmacol 14:48–58

    Google Scholar 

  14. Baron GD, Speden RN, Bohr DF (1972) Beta-adrenergic receptors in coronary and skeletal muscle arteries. Am J Physiol 223:878–881

    Google Scholar 

  15. Young MA, Vatner SF (1986) Regulation of large coronary arteries. Circ Res 59:579–596

    Google Scholar 

  16. Molenaar P, Jones CR, McMartin LR, Summers RJ (1988) Autoradiographic localization and densitometric analysis of beta-1 and beta-2 adrenoceptors in the canine left anterior descending coronary artery. J Pharmacol Exp Ther 246:384–393

    Google Scholar 

  17. Nakane T, Tsujimoto G, Hashimoto K, Chiba S (1988) Beta adrenoceptors in the canine large coronary arteries: Beta-1 adrenoceptors predominate in vasodilation. J Pharmacol Exp Ther 245:936–943

    Google Scholar 

  18. Ozaki N, Kawakita S, Toda N (1982) Effects of dobutamine on isolated canine cerebral, coronary, mesenteric, and renal arteries. J Cardiovasc Pharmacol 4:456–461

    Google Scholar 

  19. Heusch G, Deussen A (1983) The effect of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res 53:8–15

    Google Scholar 

  20. Vatner SF (1983) Alpha-adrenergic regulation of the coronary circulation in the conscious dog. Am J Cardiol 52:15A–21A

    Google Scholar 

  21. Cohen RA, Shepherd JT, Vanhoutte PM (1984) Effects of the adrenergic transmitter on epicardial coronary arteries. Fed Proc 43:2862–2866

    Google Scholar 

  22. Weiner N, Taylor P (1985) Neurohumoral transmission: The autonomic and somatic motor nervous systems. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) The pharmacological basis of therapeutics, 7th edn. MacMillan, Oxford, pp 66–96

    Google Scholar 

  23. Ariens EJ (1963) Steric structure and activity of catecholamines on α- and β-receptors. In: Brunings KJ (ed) Proceedings of the first international pharmacological meeting. Pergamon, Oxford, pp 247–264 (Modern concepts in the relationship between structure and pharmacological activity vol. 7)

    Google Scholar 

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Aikawa, J., Moroi, M., Namiki, A. et al. Vascular relaxing mechanism of denopamine in isolated canine coronary, femoral, mesenteric, and renal arteries. Heart Vessels 8, 176–180 (1993). https://doi.org/10.1007/BF01744739

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