Is There a Role for Other Ca2 Mobilizing Messengers in Hypoxic Pulmonary Vasoconstriction

We have recently demonstrated that nicotinic acid adenine dinucleotide phosphate (NAADP), a P-NADP+ metabolite (37), is a potent Ca2+mobilizing messenger in pulmonary artery smooth muscle (6). NAADP appears to trigger spatially restricted Ca2+ bursts from a thapsigargin-insensitive store, which may be a lysosomal-related organelle (9). These 'Ca2+ bursts' are then amplified into a global Ca2+ wave by Ca2+-induced Ca2+ release (CICR) via RyRs in the SR, leading to smooth muscle contraction (6). Given that cADPR sensitizes RyRs to CICR, these findings raise the possibility that NAADP may act in concert with cADPR to promote HPV. Such tight coupling of NAADP-dependent CICR to cADPR levels could also explain the all-or-none block of HPV by the cADPR antagonist 8-bromo-cADPR (12). However, further investigations are required to determine whether or not NAADP plays a role in HPV.

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