Capacitative calcium entry as a pulmonary specific vasoconstrictor mechanism in small muscular arteries of the rat

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Abstract
(1) The effect of induction of capacitative Ca2+ entry (CCE) upon tone in small (i.d. 200-500 microm) intrapulmonary (IPA), mesenteric (MA), renal (RA), femoral (FA), and coronary arteries (CA) of the rat was examined. (2) Following incubation of IPA with 100 nm thapsigargin (Thg) in Ca2+-free physiological salt solution (PSS), a sustained contraction was observed upon reintroduction of 1.8 mm Ca2+, which was unaffected by either diltiazem (10 microm) or the reverse mode Na+/Ca2+ antiport inhibitor KB-R7943 (10 microm). An identical protocol failed to elicit contraction in MA, RA, or CA, while a small transient contraction was sometimes observed in FA. (3) The effect of this protocol on the intracellular Ca2+ concentration ([Ca2+]i) was assessed using Fura PE3-loaded IPA, MA, and FA. Reintroduction of Ca2+ into the bath solution following Thg treatment in Ca2+-free PSS caused a large, rapid, and sustained increase in [Ca2+]i in all the three types of artery. (4) 100 nm Thg induced a slowly developing noisy inward current in smooth muscle cells (SMC) isolated from IPA, which was due to an increase in the activity of single channels with a conductance of approximately 30 pS. The current had a reversal potential near 0 mV in normal PSS, and persisted when Ca2+-dependent K+ and Cl- currents were blocked; it was greatly inhibited by 1 microm La3+, 1 microm Gd3+, and the IP3 receptor antagonist 2-APB (75 microm), and by replacement of extracellular cations by NMDG+. (5) In conclusion, depletion of intracellular Ca2+ stores with Thg caused capacitative Ca2+ entry in rat small muscular IPA, MA, and FA. However, a corresponding contraction was observed only in IPA. CCE in IPA was associated with the development of a small La3+- and Gd3+-sensitive current, and an increased Mn2+ quench of Fura PE-3 fluorescence. These results suggest that although CCE occurs in a number of types of small arteries, its coupling to contraction appears to be of particular importance in pulmonary arteries.