L-Type calcium channel blockers modulate the microvascular hyperpermeability induced by platelet-activating factor in vivo

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Abstract

Purpose: Platelet-activating factor (PAF) is a potent phospholipid mediator of the microvascular dysfunction associated with ischemia-reperfusion injury. Because changes in cytosolic-free Ca2+ concentration are essential in PAF cellular signaling, we formulated the hypothesis that blockade of Ca2+ entry may inhibit the PAF-induced microvascular dysfunction. Methods: To investigate this hypothesis two L-type calcium channel blockers, verapamil and nifedipine, were applied to the hamster cheek pouch before the topical PAF challenge was undertaken. Permeability was assessed by measurement of the plasma clearance of fluorescein isothiocyanate dextran, 150,000 mol wt. The arteriolar diameter was measured simultaneously to evaluate the effects of L-type calcium channel blockers on PAF-induced vasoconstriction. Results: Baseline clearance was 498.7 ± 225.0 nl/60 min/gm (mean ± SE). PAF at 10-8 mol/L (n = 5) increased clearance to 3753.8 ± 572.8 nl/60 min/gm (p < 0.01). Pretreatment with verapamil (2 mg/kg; n = 5) significantly reduced the increase in permeability caused by 10-8 mol/L PAF (1909.1 ± 620.2 nl/60 min/gm; p < 0.05). Nifedipine (5 - 10-6 mol/L; n = 5) also significantly attenuated the impact of 10-8 mol/L PAF (2037.2 ± 427.5 nl/60 min/gm; p < 0.05). Neither verapamil nor nifedipine affected PAF-induced vasoconstriction. Conclusion: The significant inhibition of the increase in permeability by the L-type calcium channel blockers suggests that these compounds may be useful in the management of PAF-induced hyperpermeability. (J VASC SURG 1995;22:732-41.). © 1995 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter.

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Oshiro, H., Kobayashi, I., Kim, D., Takenaka, H., Hobson, R. W., & Durán, W. N. (1995). L-Type calcium channel blockers modulate the microvascular hyperpermeability induced by platelet-activating factor in vivo. Journal of Vascular Surgery, 22(6), 732–741. https://doi.org/10.1016/S0741-5214(95)70064-1

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