Does cAMP attenuate ATP-induced microvessel permeability by reducing the initial increase in endothelial cell cytoplasmic Ca2+ concentration in frog mesentery microvessels?
cAMP attenuates ATP-induced microvessel permeability without modifying the initial calcium transient in endothelial cells, demonstrating that increased intracellular calcium is not always associated with increased permeability.
We investigated the hypothesis that one of the actions of adenosine 3',5'-cyclic monophosphate (cAMP) to attenuate agonist-induced increase in microvessel permeability is to reduce the initial increase in endothelial cell cytoplasmic Ca2+ concentration (Ca2+i). ATP (10 microM) was used to increase hydraulic conductivity (Lp) and Ca2+i in venular microvessel in frog mesentery. The cAMP analogue, 8-bromo-cAMP (8-BrcAMP, 2 mM) significantly attenuated the initial increase in Lp (from a peak increase of 7.1 +/- 2.4 times control with ATP alone to 1.2 +/- 0.34 times control with ATP and cAMP). In contrast, cAMP did not significantly change the magnitude or time course of the biphasic increase in Ca2+i, which increased from 54 +/- 5 nM to peak of 187 +/- 48 nM with ATP alone, and from 55 +/- 8 nM to 190 +/- 28 nM with ATP and cAMP. Thus the action of cAMP to attenuate microvessel permeability increase in the presence of ATP does not involve modification of the initial Ca2+ transient in endothelial cells. Our results enable alternative hypotheses, such as the suggestion that cAMP might modulate a Ca(2+)-calmodulin-dependent actin-myosin cascade, to be investigated without the added complications of having to account for the modulation of initial changes in Ca2+i. Our data also demonstrate, for the first time in the endothelial cells of intact microvessels, that an increase in Ca2+i is not always associated with an increase in microvessel permeability.
He et al. (Wed,) studied this question.