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Title: Synergistic effect of nisoldipine and nitroglycerin on human internal mammary artery.
Austin Authors: Liu, J J;Johnston, Colin I;Buxton, Brian F 
Affiliation: Department of Cardiac Surgery, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jan-1994
Publication information: The Journal of Pharmacology and Experimental Therapeutics; 268(1): 434-40
Abstract: Perioperative spasm of the internal mammary artery (IMA) can be a problem in coronary artery bypass surgery, which may be prevented by vasodilator drugs. The relaxing effect of a new calcium antagonist nisoldipine used alone or in combination with nitroglycerin (NTG) was studied in human isolated IMA in organ chambers. The results showed that nisoldipine exhibited a potent relaxing effect on IMA precontracted by membrane depolarization (K+ induced) with an EC50 of 7.58 +/- 0.08 (-log M). Nisoldipine was about 10 times more potent than was nifedipine (EC50, 6.72 +/- 0.10). However, both calcium antagonists showed much less relaxing effect on IMA precontracted with the thromboxane mimetic U46619. When IMA was pretreated with nisoldipine, this drug (range, 10-300 nM) inhibited contraction induced by either K+ or U46619 in a concentration-dependent manner. The relaxing effect of nisoldipine was long lasting and extremely hard to wash out (more than 3 hr). NTG showed a rapid and short-lasting relaxing effect on IMA precontracted with either K+ or U46619. Pretreatment of IMA with NTG had little effect for prevention of contraction to K+ or U46619. Combining nisoldipine with NTG at low concentrations (1-30 nM) produced a synergistic effect in the prevention of IMA contraction to K+ or U46619 and in relaxation of IMA precontracted with these agents. These studies reveal that combining nisoldipine with NTG combines the advantages of both and provide a scientific basis for a future clinical trial using combined nisoldipine and NTG at low concentrations for the preparation of IMA (pretreatment) to prevent IMA spasm during coronary artery bypass grafting.
Gov't Doc #: 8301585
Journal: The Journal of pharmacology and experimental therapeutics
Type: Journal Article
Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Drug Synergism
In Vitro Techniques
Mammary Arteries.drug effects.physiology
Muscle Relaxation.drug effects
Prostaglandin Endoperoxides, Synthetic.pharmacology
Thromboxane A2.analogs & derivatives.pharmacology
Vasoconstriction.drug effects
Vasoconstrictor Agents.pharmacology
Appears in Collections:Journal articles

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