Hypoxic contractile response in isolated human pulmonary artery: role of calcium ion

Abstract

The mechanism for hypoxic pulmonary vasoconstriction (HPVC) was investigated in human pulmonary arterial strips. Hypoxia in the presence of histamine (10(-6) M) caused marked pulmonary arterial contraction, which was reversed by O2. The hypoxic contraction in the presence of histamine was inhibited by diphenhydramine, but not by cimetidine. The hypoxic histamine-mediated contraction was attenuated but still present in the absence of extracellular Ca2+, or by the inhibitors of voltage-dependent Ca2+ influx. However, it was inhibited significantly by a further depletion of intracellular Ca2+, or by HA 1004, an intracellular calcium antagonist. A low concentration (10(-7) M) of a calcium ionophore, A23187, enhanced the hypoxic contraction in the presence of histamine, whereas procaine completely inhibited it. W-7, a calmodulin inhibitor, significantly decreased the hypoxic histamine-mediated contraction, but 12-O-tetradecanoylphorbol-13-acetate (TPA), a C-kinase promotor, had no effect. The hypoxic contractile response was also observed in the presence of both A23187 and KCl instead of histamine, but the hypoxia-induced contraction with KCl alone was much smaller than that. These results indicate that hypoxia in the presence of certain other vasoactive agents has a potent contractile effect on the human pulmonary artery and that the response is dependent on Ca2+. Enhancement of both Ca2+ influx and Ca2+ release from intracellular storage sites by hypoxia, which interacts with calmodulin, were suggested to be involved in the mechanism of HPVC.

5-Hydroxytryptamine Induces Vasoconstriction of the Human Umbilical Artery: Effects of Hypoxia and Nicorandil

“…This study shows that hypoxia does not affect the basal tone of umbilical smooth muscle, and this agrees with Hoshino et al [17], who stated that hypoxia alone did not alter the resting force. In this study, hypoxia decreased the contraction response to 5-hydroxytryptamine of the umbilical artery.…”

Response to hypoxia of pulmonary arteries in chronic obstructive pulmonary disease: anin vitrostudy

“…In vitro studies, where pulmonary artery rings are exposed to hypoxia, have only been conducted in series of patients with undefined respiratory disease [7][8][9]. To the current authors9 knowledge, there are no studies where the profile of the response to hypoxic stimulus in pulmonary arteries of COPD patients had been characterised in vitro.…”

The Effect of Hydrogen Peroxide on Hypoxia, Prostaglandin F2αand Potassium Chloride Induced Contractions in Isolated Rat Pulmonary Arteries

“…Addition of a priming concentration of agents such as PGF 2 , is necessary to produce hypoxic contractions in isolated pulmonary arteries. 1,15 As PGF 2 acts by releasing Ca 2+ ions from intracellular stores, this suggests that an elevation of intracellular Ca 2+ may be necessary before any significant hypoxia-induced contraction is seen in vitro. Recent observations 19,20 also suggest that the first phase of the HPV is dependent upon an elevation in intracellular Ca 2+ .…”

“…NADPH oxidase Hypoxic pulmonary vasoconstriction (HPV) 1 is a is a multi subunit enzyme 4 which produces superoxide regulatory mechanism within the lung, necessary for radicals from molecular oxygen. 5 Subsequent reaction the maintenance of correct ventilation/perfusion (V/Q) with water results in the formation of hydrogen perratios.…”

“…11,12 Consequently this enzyme may now also of PGF 2 . 1,13,15 Consequently, a low concentration of be considered as a potential oxygen sensor.…”