Interactions between vasodilator drugs and human hemoglobin.
1. The in vitro effect of the vasodilators papaverine, dipyridamole, nifedipine, prenylamine and glyceryl di-, tri- and tetranitrate on the oxygen saturation curve of human hemoglobin (Hb) was evaluated. The Hb dissociation curve was measured spectrophotometrically both for freshly obtained heparinized blood and for purified Hb A after incubation with the drugs. 2. For both purified Hb and whole blood samples, incubation with papaverine, dipyridamole and nifedipine modified P50 (PO2 for half saturation of the Hb/oxygen sites) at pH 7.4: 30.9 mmHg for 0.72 mM papaverine vs 23.9 mmHg for control; 23.9 mmHg for 1.43 mM dipyridamole vs 20.8 mmHg for control; 1.09 mmHg for 2.73 mM nifedipine vs 1.14 mmHg for control stripped Hb. The effects of the three vasodilators on Hb were correlated with pH, methemoglobin formation, temperature and incubation time. 3. P50 values were determined for Hb of the blood of angina patients treated with one of the vasodilators, and blood 2,3-diphosphoglycerate (2,3-DPG) levels were also measured. In contrast to the in vitro data, neither P50 nor 2,3-DPG levels were significantly modified in the blood of patients treated with one of the vasodilators. 4. These in vitro studies demonstrated that the vasodilators papaverine and dipyridamole decrease, and nifedipine increases the oxygen affinity of Hb in red blood cells or as a purified hemoglobin.
de-Paula
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Departamento de Bioquímica, Universidade Estadual de Campinas, SP, Brasil.
Meirelles
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NC
D019794:2,3-Diphosphoglycerate; D000328:Adult; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy; D004163:Diphosphoglyceric Acids / Q000097:blood; D004347:Drug Interactions; D005260:Female; D006441:Hemoglobin A / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D010108:Oxyhemoglobins / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014665:Vasodilator Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D010108:Oxyhemoglobins; D014665:Vasodilator Agents; D019794:2,3-Diphosphoglycerate; D006441:Hemoglobin A