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 microM 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 (Lp) of the microvessel wall was 5.7 +/- 0.5-fold relative to control. After removal of extracellular Ca2+, there was no significant increase in Lp, 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 Lp 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].
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Department of Human Physiology, School of Medicine, University of California, Davis 95616, USA.
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Curry
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D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D009994:Osmolar Concentration; D011894:Rana pipiens; D011956:Receptors, Cell Surface / Q000502:physiology*; D013152:Splanchnic Circulation / Q000187:drug effects
D015220:Calcium Channels; D011956:Receptors, Cell Surface; D000255:Adenosine Triphosphate; D000241:Adenosine; D001920:Bradykinin; D002118:Calcium