Atriopeptin-induced increases in endothelial cell permeability are associated with elevated cGMP levels.
To investigate the mechanism of nonrenal capillary hyperfiltration, we studied the effect of atriopeptin (AP) III and AP I on permeability and intracellular cyclic nucleotide levels in cultured bovine pulmonary artery endothelial cell monolayers. Permeability to albumin was assessed by the albumin transfer rate across endothelial cell monolayers, following a 4-h incubation with atriopeptins. AP III (0.01, 0.1, and 1 microM) caused a concentration-dependent increase in the albumin transfer rate. AP III induced a threefold increase in intracellular guanosine 3',5'-cyclic monophosphate (cGMP) levels during the incubation period. A phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), enhanced the AP III-induced increase in permeability and cGMP accumulation by 16-fold at maximum. 8-Bromoguanosine 3',5'-cyclic monophosphate, a hydrolysis-resistant cGMP analogue, caused a slight but significant increase in permeability. In contrast, AP I, a weak agonist of the cGMP-coupled ANP receptor, did not elicit an increase in permeability at concentrations of 0.1 and 1 microM. Although AP I (1 microM) caused a significant increase in cGMP by 33 and 60% in the absence and presence of IBMX, the increase was markedly less compared with AP III. AP III did not cause a change in intracellular cAMP levels during the incubation period. These observations suggest that in our system AP III increases the permeability of endothelial cell monolayers in association with an elevated cGMP level. Thus an increase in permeability might be involved in the mechanism of ANP-induced capillary hyperfiltration.
Yonemaru
M
M
Department of Medicine, Stanford University School of Medicine, California 94305.
Ishii
K
K
Murad
F
F
Raffin
T A
TA
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002199:Capillary Permeability; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments
D010446:Peptide Fragments; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; C062522:atrial natriuretic factor prohormone (103-123); D000242:Cyclic AMP; D006152:Cyclic GMP