Ca²⁺ entry through conductive pathway modulates receptor-mediated increase in microvessel permeability

We investigated the relationship between receptor-mediated increases in cytoplasmic Ca²⁺ concentration ([Ca²⁺](i)) and increased microvessel permeability. In individually perfused venular microvessels of frog mesentery exposed to 10 μM ATP, [Ca²⁺](i) increased from 59 ± 7 to 172 ± 21 nM within 1 min and then fell back toward control values. The corresponding peak increase in the hydraulic conductivity (L(p)) of the microvessel wall was 5.7 ± 0.5-fold relative to control. After removal of extracellular Ca²⁺, there was no significant increase in L(p), and the initial increase in [Ca²⁺](i) was attenuated but not abolished. Depolarization of the endothelial cell membrane with high-K⁺ Ringer solution reduced the peak increase in [Ca²⁺](i) to 106 ± 7 nM and attenuated the increase in L(p), 1.8 ± 0.4- fold. The results conform to the hypothesis that Ca²⁺ entry into endothelial cells is required for acute increase in venular microvessel permeability by inflammatory agents and that the pathway for Ca²⁺ entry has the properties of a passive conductance pathway. Similar conclusions were reached in previous experiments in frog microvessels exposed to Ca²⁺ ionophores and perfusates with no plasma proteins. In venular microvessels of hamster mesentery exposed to ATP and bradykinin, a similar pathway for Ca²⁺ entry was demonstrated in the present experiments. We did not measure permeability changes in hamster microvessels in this study, but these microvessels respond to histamine and ionophores with a transient increase in permeability to macromolecules similar to that measured in frog microvessels [Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1982-H1991, 1995].