title: Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules.
abstract: 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 microgram/g compared with 5.3 +/- 0.7 microgram/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 microliter in control sites to 9.9 +/- 2.5, 17.0 +/- 2.4, 24.3 +/- 5.9, and 23.3 +/- 5.4 microliter in sites injected with 10(-10), 10(-9), 10(-8), or 10(-7.2) 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 micrometer 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.
authors.affiliation: Clinical Pharmacology Department, United Medical and Dental Schools, St. Thomas' Hospital, London SE1 7EH, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Taherzadeh
authors.forename: A K
authors.initials: AK
authors.lastname: Das
authors.forename: J B
authors.initials: JB
authors.lastname: Warren
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents; D006801:Humans; D007211:Indoles; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D009942:Organometallic Compounds; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000493:pharmacokinetics; D012867:Skin / Q000098:blood supply*; D014699:Venules / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D004396:Coloring Agents; D007211:Indoles; D009942:Organometallic Compounds; D012709:Serum Albumin; C015445:copper phthalocyanine; D009543:Nifedipine