Rate constants suggest three mechanisms for porcine pulmonary arterial (PPA) contraction

Abstract

Vascular Smooth Muscle (VSM) uses both extracellular calcium ([Ca2+]o) and intracellular stores of calcium to signal a typical contraction. In contrast we find that fourth generation porcine pulmonary artery (PPA) contracts after high potassium depolarization with and without the presence of [Ca2+]o. The contractile behavior of PPA was modeled using JSIM Physiome Modeling software. PPA contraction in the presence of [Ca2+]o was characterized by both a fast and slow rate constant, whereas only a slow rate constant was observed without the presence of [Ca2+]o. Only this slow rate constant was detected in the presence of various calcium influx inhibitors including tetrandrine, caffeine and ethylene glycol tetraacetic acid (EGTA). High potassium‐induced contraction of PPA, with either the absence of [Ca2+]o or the inhibition of Ca2+ entry via voltage gated Ca2+ channels (VOCCs), suggests either the use of intracellular stores of Ca2+ through a novel signal transduction pathway or an unknown Ca2+ independent mechanism for contraction. PPA also contracted using H2O2, but with contractile rate that differed from those previously observed. The rates calculated from 3 mM H2O2 contractions were intermediate, but did not fit the exponential curve for the fast and slow rate constants. The intermediate curve was also dependent on [H2O2]. The intermediate rate constants suggest an alternative third mechanism underlying PPA contraction in response to H2O2.