EFFECT OF NITRATE TOLERANCE AND DIPYRIDAMOLE ON THE RESPONSE TO SIN1 IN THE HUMAN ISOLATED SAPHENOUS-VEIN

被引:15
作者
BOHYN, M [1 ]
BERKENBOOM, G [1 ]
FONTAINE, J [1 ]
机构
[1] HOP ERASMUS,DEPT CARDIOL,ROUTE LENNIK 808,B-1070 BRUSSELS,BELGIUM
关键词
NITRATE TOLERANCE; SIN1; DIPYRIDAMOLE; VENA SAPHENA MAGNA;
D O I
10.1007/BF03029770
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The relaxant effects of nitroglycerin (NTG) and SIN1 on human vena saphena magna were studied in vitro. Nitrate tolerance was produced after incubation of the preparation with nitroglycerin (NTG 10-mu-M for 10 minutes). Vessels precontracted by serotonin (0.25-mu-M) and made tolerant to NTG exhibited a slight but significant shift (p < 0.01) to the right of the dose-response curve to SIN1 (EC50 increased from 1.12 +/- 0.21-mu-M to 2.74 +/- 0.32-mu-M). The maximal relaxation was unaltered. On the contrary, there was a marked attentuation of the maximal relaxation to NTG in the nitratetolerant preparation (maximal relaxation decreased from 73 +/- 2% to 35 +/- 1%). Dipyridamole, a phosphodiesterase (PDe) inhibitor, significantly potentiated the responses to SIN1 on control rings (EC50 = 57.1 +/- 1.8 nM), and on NTG-tolerant rings it reversed the responsiveness to SIN1 (EC50 = 88.9 +/- 9.2 nM), which suggests that nitrate tolerance may be partially due to an increase in PDe activity. In conclusion we have demonstrated a slight cross-tolerance between SIN1 and NTG on human vena saphena magna. Nevertheless, after induction of in vitro NTG tolerance, the attentuation of responses to SIN1 is much less pronounced that the alteration of NTG relaxations.
引用
收藏
页码:457 / 461
页数:5
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  • [1] Kukovetz W.R., Holzmann S., Mechanism of vasodilation by Molsidomine, Am Heart J, 109, pp. 637-640, (1985)
  • [2] Kukovetz W.R., Holzmann S., Cyclic GMP as the mediator of Molsidomine-induced vasodilatation, Eur J Pharmacol, 122, pp. 103-109, (1986)
  • [3] Berkenboom G., Fontaine J., Degre S., Persistence of the response to SIN<sub>1</sub> on isolated coronary arteries rendered tolerant to nitroglycerin in vitro or in vivo, J Cardiovasc Pharmacol, 12, pp. 345-349, (1988)
  • [4] Inhof P.R., Ott B., Frankhause P., Et al., Difference in nitroglycerin dose-response in the venous and arterial beds, Eur J Clin Pharmacol, 18, pp. 455-460, (1980)
  • [5] Mackenzie J.E., Parratt J.R., Comparative effects of glyceryl trinitrate on venous and arterial smooth muscle in vitro
  • [6] relevance to antianginal activity, Br J Pharmacol, 60, pp. 155-160, (1977)
  • [7] Atrong P.W., Atrong J.A., Macks G.S., Pharmacokinetichemodynamic studies of intravenous nitroglycerin in congestive cardiac failure, Circulation, 62, pp. 160-166, (1980)
  • [8] Ahlner J., Anderson R.G., Axelsson K.L., Et al., Development of tolerance to glyceryl trinitrate in an isolated human peripheral vein and its relation to cyclic GMP metabolism, Acta Pharmacol Toxicol, 59, pp. 123-128, (1986)
  • [9] Axelsson K.L., Karlsson J.O.G., Nitroglycerin tolerance in vitro: Effect on cGMP turnover in vascular smooth muscle, Acta Pharmacol Toxicol, 55, pp. 203-210, (1984)
  • [10] Edwards J.C., Ignarro L.J., Hyman A.L., Kadovitz P.J., Relaxation of intrapulmonary artery and vein by nitrogen oxidecontaining vasodilators and cyclic cGMP, J Pharmacol Exp Therap, 228, pp. 33-42, (1984)