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

We investigated the rela-tionship 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 l 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 arid 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].