Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules
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- Morteza Taherzadeh
- Clinical Pharmacology Department and
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- Asit K. Das
- Histopathology Department, United Medical and Dental Schools, St. Thomas’ Hospital, London SE1 7EH, United Kingdom
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- John B. Warren
- Clinical Pharmacology Department and
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説明
<jats:p> Calcium-channel antagonist drugs are prescribed widely for angina and hypertension. A limiting side effect is edema, which can make heart failure worse. We show that nifedipine, a dihydropyridine-type calcium-channel antagonist, can increase vascular permeability in rat skeletal muscle and skin when injected locally. In nifedipine-injected cremaster muscle, the copper content, used to quantify Monastral blue dye accumulation, was 15.0 ± 2.4 μg/g compared with 5.3 ± 0.7 μg/g in control preparations ( P < 0.05). The injection of nifedipine in rat skin in vivo increased local plasma leakage in injected sites from 5.5 ± 1.1 μl in control sites to 9.9 ± 2.5, 17.0 ± 2.4, 24.3 ± 5.9, and 23.3 ± 5.4 μl in sites injected with 10<jats:sup>−10</jats:sup>, 10<jats:sup>−9</jats:sup>, 10<jats:sup>−8</jats:sup>, or 10<jats:sup>−7.2</jats:sup> mol/site, respectively ( P < 0.05 in each case compared with control). Vascular labeling techniques using light microscopy, electron microscopy, and microanalysis show that the microvascular site of leakage is not from capillaries but from postcapillary venules of 12–36 μm in diameter, the same site that controls the edema response in inflammation. Nifedipine can act within the microcirculation to increase the permeability of the postcapillary venule. </jats:p>
収録刊行物
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- American Journal of Physiology-Heart and Circulatory Physiology
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American Journal of Physiology-Heart and Circulatory Physiology 275 (4), H1388-H1394, 1998-10-01
American Physiological Society