title: Cardiac inotropes inhibit the oedema caused by nifedipine in rabbit skin.
abstract: 1. We have shown previously that exposing the rat or rabbit microcirculation to nifedipine increases the permeability of the post-capillary venule, the segment of microcirculation that is known to control inflammatory oedema. 2. In the present study modulation by the inotropes isoprenaline, dopexamine and dobutamine of nifedipine-induced oedema was examined in the rabbit skin microcirculation by measuring the localised leakage of 125I-radiolabelled albumin after the i.d. injection of agents. 3. Coinjection of isoprenaline (10(-11) moles per site), dopexamine (10(-10) moles per site) or dobutamine (10(-10) moles per site) suppressed significantly (P < 0.05) the oedema response to nifedipine (10(-7.2) moles per site) in the rabbit dorsal skin microcirculation. 4. To confirm the oedema suppresser effect of the inotropes, dopexamine or dobutamine were also coinjected with histamine 10(-8) + PGE2 10(-10) moles per site, or bradykinin 10(-10) + PGE2 10(-10) moles per site. Both inotropes at 10(-10) moles per site reduced significantly (P < 0.05) the leakage of albumin caused by bradykinin + PGE2 and histamine + PGE2. 5. When measured by laser Doppler, basal local skin blood flow increased at 30 min by 57 +/- 14% with nifedipine 10(-7.2) moles per site and 15 +/- 11% with isoprenaline 10(-11) moles per site. Isoprenaline did not suppress the blood flow response to nifedipine, the response to coinjection being 68 +/- 11%. 6. Oedema caused by nifedipine can be suppressed by low concentrations of beta-adrenergic agonists that do not suppress the blood flow response to nifedipine. This suggests that cardiac inotropes can influence non-inflammatory changes in microvascular permeability.
authors.affiliation: Department of Clinical Pharmacology, UMDS, St Thomas' Hospital, London.
authors.forename: M
authors.initials: M
authors.lastname: Taherzadeh
authors.forename: J B
authors.initials: JB
authors.lastname: Warren
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D006632:Histamine / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009543:Nifedipine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011817:Rabbits; D012867:Skin / Q000098:blood supply / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; C046318:dopexamine; D004280:Dobutamine; D006632:Histamine; D009543:Nifedipine; D015232:Dinoprostone; D007545:Isoproterenol; D001920:Bradykinin; D004298:Dopamine