Potential greater than additive vasorelaxant actions of milrinone and nitroglycerin on human conduit arteries

摘要

1 The mechanism of vasorelaxation for phosphodiesterase III inhibitors is mediated by increase of cAMP whereas for nitrovasodilators, cGMP. The purpose of this study was to test the hypothesis that the phosphodiesterase I inhibitor milrinone and nitroglycerin (NTG) may have greater than additive effects in human arteries. 2 Internal mammary artery segments (IMA, n = 90) taken from 23 patients were studied in organ chambers. The effect of milrinone (3 μM), NTG (10 nM), or the combination was tested in IMA rings precontracted with potassium (K ⁺ , 25 mM) or U46619 (10 nM). Concentration-contraction curves for K ⁺ or U46619 were established in other rings treated with milrinone (70 μM), NTG (0.1 μM), or the combination for 10 min. 3 In K ⁺ -induced contraction, the combination produced more relaxation (45.4%) than did either milrinone (7.9%, P + -induced contraction and to NTG alone (P 50 rightward and this shift was significantly more than that caused by treatment with NTG alone (P 4 We conclude that there is a greater than additive vasorelaxant effect of PDE III inhibitors and nitrovasodilators in human conduit arteries. This effect may be beneficial to patients undergoing coronary artery bypass grafting and to other patients requiring these vasodilators. Reduced doses of the vasodilators in concentration may be sufficient to produce vasodilatation similar to that produced by either of them alone at higher concentrations.