Action of the stable prostacyclin analogue iloprost on microvascular tone and -permeability in the hamster cheek pouch

Abstract

In order to further elucidate the mechanisms involved in therapeutic effects of prostacyclin and Iloprost in peripheral ischemic disease, the actions on microvascular tone, capillary density, and increases in venular permeability induced by inflammatory mediators and by ischemia were investigated in the cheek pouch of anaesthetized Syrian hamsters using intravital videomicroscopy and - for quantification of vascular permeability - venular leakage of fluorescein-labelled dextran (FITC-D; Mw 70,000). Iloprost at the nonhypotensive, platelet aggregation-inhibiting dose of 0.5 μg/kg/min i.v. significantly increased the diameters of arterioles and venules and the density of perfused capillaries and antagonized vasoconstriction and decrease of perfused capillary density as induced by Leukotriene D₄ (LTD₄; 10⁻⁷ M). Iloprost significantly antagonized venular leakage of FITC-D induced by histamine (10⁻⁵ M), serotonin (10⁻⁵ M), bradykinin (10⁻⁶ M) and reperfusion after 30 min ischemia. Topical application of Iloprost (10⁻⁸ M), intraarterial infusion of Prostaglandin E₁ (PGE₁; 2.0 μg/kg/min), and topical Forskolin (10⁻⁵ M) also attenuated histamine-induced venular FITC-D leakage, while topical PGE₁ (10⁻⁷M) and i.v. infusion of Nifedipine (30 μg/kg + 10 μg/kg/min) were not effective.

It is concluded, that microvascular effects of Iloprost by improvement of tissue perfusion and functional antagonism of mediator-induced tissue edema and vasospasm could contribute to therapeutic effectiveness in ischemic diseases.