Dual role of cgmp in modulation of macromolecule permeability of
aortic endothelial cells.
H[diaeresis]olschermann, H., T. Noll, A. Hempel, H. M. Piper.
Physiologisches Institut, Justus-Liebig-Universit[umlaut]at, Aulweg
129, D-35392 Gie[beta]en, Germany
APStracts 3:0357H, 1996.
The effect of the guanosine-3_,5_-cyclic monophosphate (cGMP) on
cytosolic calcium (Cai) dynamics and associated alterations in
macromolecule permeability was investigated in cultured monolayers of
aortic endothelial cells. Addition of the membrane-permeable cGMP
analogue 8-Br-cGMP (5 x 10-4 M) or activators of the soluble (3
-morpholinosydnonimine, SIN-1; 10-5 M) or the particulate guanylyl
cyclase (atrial natriuretic peptide, ANP; 10-7 M) to unstimulated
monolayers led to a decrease in permeability (8-Br-cGMP: 62 +/- 8% of
control) without affecting low basal Cai (87 +/- 8 nM). In contrast,
under conditions of elevated Cai (503 +/- 95 nM) and increased
permeability (155 +/- 7% of control) induced by ionomycin (10-6 M),
8-Br-cGMP, SIN-1 or ANP provoked a further increase in permeability
(8-Br-cGMP: 255 +/- 27%). These agents failed to increase
permeability when added prior or subsequently to the ionomycin
-triggered transitory Cai rise. The increase in permeability in
response to 8-Br-cGMP was due to a secondary further rise of Cai (758
+/- 87 nM) which was abolished in absence of extracellular Ca2+,
indicating influx of exogenous Ca2+ as the cause. Both changes in Cai
and permeability were inhibited in the presence of Rp-8-pCPT-cGMPs (2
x10-5 M), an inhibitor of the cGMP-dependent protein kinase. These
findings show that, depending on cytosolic Ca2+ concentration, cGMP
can play opposite roles on endothelial permeability in one and the
same cell preparation.
Received 14 February 1996; accepted in final form 30 July 1996.
APS Manuscript Number H151-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996