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Autori: Dospinescu C, Yamawaki N, McCaig D, Wainwright CL, Cruickshank SF
Editorial: J Physiol 568P, p.PC44, 2005.
In the pulmonary artery (PA), hypoxia releases Ca2+ from the SR (Dipp et al. 2001) and during hypoxia, Ca2+ released from the SR may activate the Ca2+-activated Cl- channel (ClCa) in the plasma membrane (Wang et al. 1997). Decreasing [Cl-]o can increase agonist-induced contraction in the PA (Lamb & Barna, 1998).
Here we report the effects of decreasing [Cl-]o on the hypoxic pulmonary vasoconstriction (HPV) response in preconstricted porcine PA. Porcine lungs were obtained from a local abattoir. Pulmonary arteries (4th-5th order) were dissected free (external diameter 500-800 microm), mounted in a myograph and resting tone set at 2mN. Hepes-based PSS were made hypoxic by aerating with N2 and PO2 monitored continuously. In low Cl- solutions, NaCl was replaced with equimolar Na-gluconate. Pre-tone was achieved using 2 microM PGF2alpha. Endothelial function was assessed by determining the ability of 20microM ACh to relax KCl-constricted vessels. All drugs were bath applied. Where appropriate, data are expressed as a % of KCl-induced contraction and presented as mean values +- S.E.M. Significance was determined at P< 0.05 using a Student's paired or unpaired t test as appropriate. Control contractions were induced using 80 mM KCl (14.4 +- 2.8 mN, n=6). PGF2alpha-induced contractions were 1.4 +- 1% of control response. Hypoxia (PO2 < 25 mm Hg) resulted in a slow monophasic increase in tone (13.4 +- 3.6% of control), which was reversible on return to normoxia. In low-Cl- solution, hypoxia-induced contractions were significantly increased (41.5 +- 9.8% of control; P< 0.05 compared to Cl--containing bath solution, n=6). In Ca2+-free solution, the hypoxic response (15.9 +- 5.3% of control) was not significantly different compared to hypoxic, normal Cl- solution, (P> 0.05, n=6). There was no significant difference between endothelial (+) and endothelial (-) vessels in the contractile response to hypoxia, either in normal Cl- or low-Cl- solution (P> 0.05). Hypoxia-induced contractions returned to resting tone upon washout with normoxic normal Cl- solution (1.6 +- 0.3 mN). Washout with normoxic, low-Cl- solution only resulted in a partial relaxation to baseline (5.1 +- 0.6 mN, P< 0.05, n=5). Increased tone in low-Cl-, normoxic solution was insensitive to the Ca2+ channel blocker nifedipine (5microM) but was sensitive to the Cl- channel blocker niflumic acid (50 microM). These data suggest a role for ClCa in modulating the porcine HPV response and resting tone in pre-stimulated porcine PA.
Cuvinte cheie: hypoxic pulmonary vasoconstriction, chloride