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

1 The effect of induction of capacitative Ca2+ entry (CCE) upon tone in small (i.d. 200-500 mum) 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 muM) or the reverse mode Na+/Ca2+ antiport inhibitor KB-R7943 (10 muM). 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 similar to 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 muM La3+, 1 muM Gd3+, and the IP3 receptor antagonist 2-APB (75 muM), 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.