Cardiac inotropes inhibit the oedema caused by nifedipine in rabbit skin.
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.
Taherzadeh
M
M
Department of Clinical Pharmacology, UMDS, St Thomas' Hospital, London.
Warren
J B
JB
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*
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; C046318:dopexamine; D004280:Dobutamine; D006632:Histamine; D009543:Nifedipine; D015232:Dinoprostone; D007545:Isoproterenol; D001920:Bradykinin; D004298:Dopamine