Microvascular permeability and number of tight junctions are modulated by cAMP

• Published in: American journal of physiology. Heart and circulatory physiology 1998-06, Vol.274 (6), p.H1885-H1894
• Main Authors: Adamson, R. H, Liu, B, Fry, G. Nilson, Rubin, L. L, Curry, F. E
• Format: Article
• Language: English
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.1998.274.6.h1885

1  Department of Human Physiology, School of Medicine, University of California, Davis, California 95616; and 2  Eisai London Research Laboratories, University College London, London WC1E 6BT, United Kingdom We tested the hypothesis that increased endothelial cell adenosine 3',5'-cyclic monophosphate (cAMP) decreases microvascular permeability in vivo. The effects of cAMP-specific phosphodiesterase type IV inhibition and adenylate cyclase activation on microvascular hydraulic conductivity ( L p ) were investigated in intact individual capillaries and postcapillary venules in mesentery of pithed frogs ( Rana pipiens ). Treatment with rolipram (10 µM) and forskolin (5 µM) for 25 min decreased L p to 37% of control. Rolipram alone also significantly decreased L p . Isoproterenol (10 µM) decreased L p to 27% of control within 20 min. A subgroup of eight vessels treated with rolipram and forskolin, in which mean L p fell to 25% of control, was examined with transmission electron microscopy. The mean number of tight junctions in the treated vessels was 2.2 per cleft (303 clefts), significantly higher than in a matched control group (192 clefts), which was 1.7 per cleft. The results indicate that microvascular L p can be modulated by intracellular cAMP and that one of the structural end points of stimulated cAMP levels is an increase in the mean number of tight-junction strands between endothelial cells. capillary permeability; vascular endothelium; intercellular junctions; intercellular adhesion