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Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules
M Taherzadeh1, A K Das, J B Warren
1Clinical Pharmacology Department, United Medical and Dental Schools, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
The American Journal of Physiology
|September 24, 1998
Summary
Nifedipine, a calcium-channel antagonist, increases vascular permeability in rat tissues. This drug specifically enhances leakage from postcapillary venules, a key site for edema formation.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Microcirculation
Background:
- Calcium-channel antagonists are widely used for angina and hypertension.
- Edema is a common side effect that can exacerbate heart failure.
Purpose of the Study:
- To investigate the effect of nifedipine on vascular permeability.
- To identify the specific microvascular site responsible for nifedipine-induced leakage.
Main Methods:
- Local injection of nifedipine into rat cremaster muscle and skin.
- Quantification of Monastral blue dye accumulation to measure vascular leakage.
- Microvascular analysis using light and electron microscopy, and microanalysis.
Main Results:
- Nifedipine significantly increased dye accumulation in cremaster muscle and plasma leakage in skin.
- Leakage was dose-dependent, with significant increases observed at concentrations from 10(-10) mol/site.
- Microvascular analysis revealed leakage occurred from postcapillary venules (12-36 micrometer diameter).
Conclusions:
- Nifedipine increases microvascular permeability.
- The postcapillary venule is the primary site of nifedipine-induced leakage.
- These findings suggest a mechanism for nifedipine-induced edema in patients.