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Endothelium-dependent effects of platelet-activating factor in the coronary circulation
V F Sagach1, A V Zhukova, P Braquet
1A. A. Bogomoletz Institute of Physiology, Academy of Science of Ukraine, Kiev.
Insights
Platelet-activating factor (PAF) causes coronary vasodilation in dogs at low doses, but constriction at high doses. This effect is endothelium-dependent, as shown by experiments using PAF receptor antagonists.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Platelet-activating factor (PAF) is a potent mediator involved in various physiological and pathological processes.
- The role of PAF in regulating coronary blood flow and its dependence on the endothelium requires further elucidation.
Purpose of the Study:
- To investigate the dose-dependent effects of intracoronary platelet-activating factor (PAF) on canine coronary circulation.
- To determine the role of the endothelium in PAF-mediated coronary vascular responses.
Main Methods:
- Experiments were conducted on anesthetized dogs with autoperfused coronary arteries.
- Different doses of PAF were administered intracoronary, and coronary resistance (CR) and coronary blood flow (CF) were measured.
- Endothelial function was assessed after chemical de-endothelialization with saponin.
- PAF receptor antagonists (BN 52021 and WEB 2086) were used to block PAF-induced reactions.
Main Results:
- Low doses of PAF (100-200 ng/kg) induced a dose-dependent decrease in CR and increase in CF.
- Higher PAF doses (≥300 ng/kg) resulted in increased CR and decreased CF, indicating a biphasic response.
- Chemical de-endothelialization abolished PAF-induced vasodilation, causing constriction instead.
- PAF receptor antagonists completely blocked all PAF-induced coronary reactions.
Conclusions:
- PAF exerts dose-dependent effects on the canine coronary circulation, causing vasodilation at low doses and vasoconstriction at higher doses.
- PAF-induced vasodilation in the canine coronary arteries is critically dependent on the presence of functional endothelium.
- These findings highlight the complex role of PAF in regulating coronary blood flow and suggest its potential involvement in endothelial dysfunction.
Abstract:
In experiments on anesthetized dogs, the effect of intracoronary administration of different doses of platelet-activating factor (PAF) has been investigated. One of the branches of the left coronary artery was catheterized via the main carotid artery. The coronary artery was autoperfused with blood from the subclavian artery. Intracoronary administration of small doses of PAF (100 and 200 ng/kg) caused a dose-dependent decrease in coronary resistance (CR) and an increase in coronary blood flow (CF). When 200 ng/kg of PAF was used, these changes were 30 and 34% vs. control, respectively. Dose increase to 300 ng/kg led to a biphasic reaction. Intracoronary administration of larger PAF doses produced opposite effects, i.e., increase in CR and decrease in CF. Chemical de-endothelialization by saponin (5 mg/5 ml, 1.5-2 min) transformed coronary dilation to small doses of PAF to constriction. The CR rose from 2.8 +/- 0.3 to 5.6 +/- 0.9 mm Hg/ml/min (p < 0.01) and CF dropped two-fold. The PAF receptor antagonists BN 52021 (6 mg/kg) and WEB 2086 (3 mg/kg) completely abolished PAF-induced coronary reactions. Hence, PAF-induced vasodilation of the canine coronary circulation is endothelium dependent.