Related Experiment Videos
Stimulated leukocyte adhesion in coronary microcirculation is reduced by a calcium antagonist
1Department of Surgery, University of Arizona, Tucson 85724.
Insights
Nisoldipine, a calcium antagonist, reduces leukocyte adhesion in coronary capillaries during inflammation. This suggests a potential cardioprotective mechanism for dihydropyridine calcium antagonists in heart conditions.
Area of Science:
- Cardiovascular Physiology
- Inflammation Research
- Pharmacology
Background:
- Leukocyte sequestration in coronary microcirculation is an initial step in acute myocardial inflammatory responses.
- Understanding leukocyte adhesion and the impact of therapeutic agents is crucial for cardiovascular health.
Purpose of the Study:
- To identify the specific locations of stimulated leukocyte deposition within the coronary microcirculation.
- To investigate the effects of the calcium antagonist, nisoldipine, on leukocyte adhesion.
- To explore potential cardioprotective mechanisms of dihydropyridine calcium antagonists.
Main Methods:
- Leukocytes were stimulated with N-formylmethionyl-leucyl-phenylalanine (FMLP).
- In vitro leukostasis was assessed using nylon fiber columns to measure white cell adherence.
- In vivo coronary microcirculation studies evaluated leukocyte sequestration.
- Blood cell adherence was quantified with and without nisoldipine pretreatment.
Main Results:
- FMLP significantly increased granulocyte adherence in vitro (30% to 69%).
- Nisoldipine pretreatment reduced FMLP-induced adhesion to 47% in vitro.
- FMLP caused marked leukocyte sequestration in coronary capillaries in vivo.
- Nisoldipine significantly attenuated FMLP-induced leukostasis in coronary capillaries (P < 0.05).
Conclusions:
- Nisoldipine directly reduces FMLP-induced leukocyte adhesion and sequestration in the coronary microcirculation.
- The observed effects suggest a direct action of nisoldipine on blood cells, not blood vessels.
- These findings propose a novel cardioprotective mechanism for dihydropyridine calcium antagonists.
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.