NO modulates myocardial O2consumption in the nonhuman primate: an additional mechanism of action of amlodipine
| Autor: | Christopher P. A. Doe, Michael S. Wolin, Andrew H. Smith, Eric A. Wolfgang, Paul R. Forfia, Thomas H. Hintze, Delvin R. Knight, David M. Flynn, Xiaoping Zhang |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty Physiology Bradykinin In Vitro Techniques S-Nitroso-N-Acetylpenicillamine Pharmacology Nitric Oxide Nitric oxide chemistry.chemical_compound Oxygen Consumption Ramipril In vivo Physiology (medical) Internal medicine medicine Animals Nitric Oxide Donors Amlodipine Enzyme Inhibitors business.industry Myocardium Penicillamine Hemodynamics Calcium Channel Blockers In vitro Macaca fascicularis NG-Nitroarginine Methyl Ester Endocrinology Mechanism of action chemistry Circulatory system Female medicine.symptom Cardiology and Cardiovascular Medicine business Ramiprilat medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 276:H2069-H2075 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.1999.276.6.h2069 |
| Popis: | Recent evidence from our laboratory and others suggests that nitric oxide (NO) is a modulator of in vivo and in vitro oxygen consumption in the murine and canine heart. Therefore, the goal of our study was twofold: to determine whether NO modulates myocardial oxygen consumption in the nonhuman primate heart in vitro and to evaluate whether the seemingly cardioprotective actions of amlodipine may involve an NO-mediated mechanism. Using a Clark-type O2 electrode, we measured oxygen consumption in cynomologous monkey heart at baseline and after increasing doses of S-nitroso- N-acetylpenicillamine (SNAP; 10−7–10−4M), bradykinin (10−7–10−4M), ramiprilat (10−7–10−4M), and amlodipine (10−7–10−5M). SNAP (−38 ± 5.8%), bradykinin (−19 ± 3.9%), ramiprilat (−28 ± 2.3%), and amlodipine (−23 ± 4.5%) each caused significant ( P < 0.05) reductions in myocardial oxygen consumption at their highest dose. Preincubation of tissue with nitro-l-arginine methyl ester (10−4 M) blunted the effects of bradykinin (−5.4 ± 3.2%), ramiprilat (−4.8 ± 5.0%), and amlodipine (−5.3 ± 5.0%) but had no effect on the tissue response to SNAP (−38 ± 5.8%). Our results indicate that NO can reduce oxygen consumption in the primate myocardium in vitro, and they support a role for the calcium-channel blocker amlodipine as a modulator of myocardial oxygen consumption via a kinin-NO mediated mechanism. |
| Databáze: | OpenAIRE |
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