title: Stimulated leukocyte adhesion in coronary microcirculation is reduced by a calcium antagonist.
abstract: The first step in the acute myocardial inflammatory response is leukocyte sequestration in the coronary microcirculation. To determine the location(s) of stimulated leukocyte deposition in the coronary microcirculation and the effects of the calcium antagonist, nisoldipine, on leukocyte adhesion, leukocytes were stimulated with the chemotactic peptide, N-formylmethionyl-leucyl-phenylalanine (FMLP) and blood cell adherence was evaluated using two methods. In vitro leukostasis was evaluated by measuring the extraction of white cells in nylon fiber columns. We found that diluted whole blood (DWB) demonstrated 30% granulocyte adherence. The chemotactic peptide FMLP (1 microM) significantly increased adherence to 69%. Pretreatment of the blood with nisoldipine (1 microM) immediately before FMLP significantly reduced the FMLP-induced adhesion to 47%. In the coronary microcirculation, FMLP caused a marked increase in leukocyte sequestration, primarily in coronary capillaries. The FMLP effect was somewhat transient because the washout of trapped white cells was similar in the vehicle and FMLP groups. Nisoldipine significantly reduced the FMLP-induced leukostasis in coronary capillaries (P < 0.05). The magnitude of the attenuation of leukostasis with nisoldipine was remarkably similar in both models, suggesting a direct effect of this agent on the blood rather than on the blood vessels. These findings offer another possible mechanism by which dihydropyridine calcium antagonists may be cardioprotective under pathophysiological conditions.
authors.affiliation: Department of Surgery, University of Arizona, Tucson 85724.
authors.forename: P F
authors.initials: PF
authors.lastname: McDonagh
authors.forename: M J
authors.initials: MJ
authors.lastname: Rauzzino
mesh_terms: D000818:Animals; D001790:Blood Physiological Phenomena; D002448:Cell Adhesion / Q000187:drug effects; D003326:Coronary Circulation; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008833:Microcirculation; D008955:Models, Cardiovascular; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D015737:Nisoldipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015737:Nisoldipine; D009240:N-Formylmethionine Leucyl-Phenylalanine