Preferential vasodilator effects of levosimendan in resistance pulmonary arteries in a rodent pulmonary embolism model

Abstract

Background: We compared the vasoactive effects of levosimendan on isolated conduit pulmonary arteries (CPA) and resistance pulmonary arteries (RPA) versus mesenteric arteries, and we assessed the pulmonary artery (PA) vascular function and the PA vasoactive effects of levosimendan in a rodent pulmonary embolism (PE) model.Methods: One group of male Wistar rats (200-300 g) was killed by decapitation to obtain pulmonary and mesenteric rings. Another group was assigned to a massive PE or saline solution infusion. After euthanasia, mesenteric arteries and CPA (1-2 mm) and RPA (≤0.5 mm) were dissected and cut into 2-3 mm wide rings, recording contractile tension. We obtained the concentration-response curves of cumulative doses of levosimendan on pre-contracted arterial rings from decapitated and sham/embolized animals. A set of RPA rings was exposed to acute hypoxia. The effect of PE on the pulmonary vasoactive function was assessed by dose-response curves of acetylcholine (ACh) and endothelin-1 (ET-1) of PA rings from sham/embolized animals.Results: Levosimendan relaxant potency of RPA was similar to that of mesenteric arteries and higher than CPA, while mesenteric rings showed the maximal relaxant effect, followed by RPA and CPA, respectively. PE did not affect the vasoactive response of PA rings either to ACh or to ET-1, and the relaxant effects of CPA and RPA to levosimendan were also preserved. Acute hypoxia reduced (p<0.05) but did not avoid the RPA relaxant effect of levosimendan.Conclusions: Levosimendan is a more specific vasodilator of RPA with a similar relaxant potency as mesenteric arteries, which is preserved after PE but significantly reduced during hypoxia.