The FASEB Journal, Vol 7, 1394-1400, Copyright © 1993 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Opposing roles of cyclic AMP in the vascular control of edema formation

JB Warren, AJ Wilson, RK Loi and ML Coughlan
National Heart and Lung Institute, London, United Kingdom.

Eight agents that increase the intracellular concentration of cyclic AMP were tested for their effect on edema formation. The specificity of the agents for vascular smooth muscle or the endothelium was determined by measuring vasodilation with a laser Doppler flow probe and cAMP production by endothelial cells and vascular smooth muscle cells in culture. The agents were injected intradermally in anesthetized rabbit skin and the local accumulation of 125I-labeled albumin in response to intradermal bradykinin was measured. Iloprost, prostaglandin E1, prostaglandin E2, pituitary adenylate cyclase activating polypeptide (PACAP), and vasoactive intestinal polypeptide (VIP) potentiated bradykinin-induced edema. These same agents also increased blood flow and vascular smooth muscle cAMP concentrations, but did not increase endothelial cell cAMP production. Albuterol suppressed edema formation, did not cause vasodilation, but did increase endothelial cell cAMP concentrations. The phosphodiesterase inhibitor rolipram did not cause vasodilation, but suppressed edema and potentiated the cAMP response to albuterol in cultured endothelial cells. L-Isoproterenol affected both cell types. At a lower concentration L-isoproterenol was a potent stimulus to endothelial cell cAMP production and inhibited edema formation; a higher dose had additional effects on vascular smooth muscle and significantly increased blood flow. These findings support the hypothesis that increasing intracellular cAMP concentrations in vascular smooth muscle promotes edema via increased blood flow. In contrast, increasing cAMP concentrations in endothelium may suppress edema by enhancing the permeability barrier.

This article has been cited by other articles:

				G D Perkins, F Gao, and D R Thickett In vivo and in vitro effects of salbutamol on alveolar epithelial repair in acute lung injury Thorax, March 1, 2008; 63(3): 215 - 220. [Abstract] [Full Text] [PDF]

				I. Rubinstein Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is tyrosine kinase dependent J Appl Physiol, July 1, 2007; 103(1): 184 - 189. [Abstract] [Full Text] [PDF]

				M. Hautmann, U. G. Friis, M. Desch, V. Todorov, H. Castrop, F. Segerer, C. Otto, G. Schutz, and F. Schweda Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Renin Secretion via Activation of PAC1 Receptors J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1150 - 1156. [Abstract] [Full Text] [PDF]

				D. Roosterman, T. Goerge, S. W. Schneider, N. W. Bunnett, and M. Steinhoff Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev, October 1, 2006; 86(4): 1309 - 1379. [Abstract] [Full Text] [PDF]

				I. Rubinstein and S. G. Von Essen Hog barn dust extract increases macromolecular efflux from the hamster cheek pouch J Appl Physiol, July 1, 2006; 101(1): 128 - 134. [Abstract] [Full Text] [PDF]

				M. A. Crawford, C. V. Aylott, R. W. Bourdeau, and G. M. Bokoch Bacillus anthracis Toxins Inhibit Human Neutrophil NADPH Oxidase Activity. J. Immunol., June 15, 2006; 176(12): 7557 - 7565. [Abstract] [Full Text] [PDF]

				M. Steinhoff, S. Stander, S. Seeliger, J. C. Ansel, M. Schmelz, and T. Luger Modern Aspects of Cutaneous Neurogenic Inflammation Arch Dermatol, November 1, 2003; 139(11): 1479 - 1488. [Abstract] [Full Text] [PDF]

				I. Rubinstein, R. Chandilawa, S. Dagar, D. Hong, and X.-P. Gao Adenosine A1 receptors mediate plasma exudation from the oral mucosa J Appl Physiol, August 1, 2001; 91(2): 552 - 560. [Abstract] [Full Text] [PDF]

				I. Rubinstein, J. Potempa, J. Travis, and X.-P. Gao Mechanisms Mediating Porphyromonas gingivalis Gingipain RgpA-Induced Oral Mucosa Inflammation In Vivo Infect. Immun., February 1, 2001; 69(2): 1199 - 1201. [Abstract] [Full Text] [PDF]

				I. Rubinstein Subtilisin Increases Macromolecular Efflux from the Oral Mucosa Clin. Vaccine Immunol., September 1, 2000; 7(5): 794 - 802. [Abstract] [Full Text] [PDF]

				X.-P. Gao, S. R. Akhter, H. Ikezaki, D. Hong, and I. Rubinstein Dexamethasone attenuates acute macromolecular efflux increase evoked by smokeless tobacco extract J Appl Physiol, August 1, 1999; 87(2): 619 - 625. [Abstract] [Full Text] [PDF]

				S. R. Akhter, H. Ikezaki, X.-P. Gao, and I. Rubinstein Dexamethasone attenuates grain sorghum dust extract-induced increase in macromolecular efflux in vivo J Appl Physiol, May 1, 1999; 86(5): 1603 - 1609. [Abstract] [Full Text] [PDF]

				M. Taherzadeh, A. K. Das, and J. B. Warren Nifedipine increases microvascular permeability via a direct local effect on postcapillary venules Am J Physiol Heart Circ Physiol, October 1, 1998; 275(4): H1388 - H1394. [Abstract] [Full Text] [PDF]

				X.-P. Gao Grain sorghum dust increases macromolecular efflux from the in situ nasal mucosa J Appl Physiol, April 1, 1998; 84(4): 1431 - 1436. [Abstract] [Full Text] [PDF]

				X.-P. Gao, S. R. Akhter, and I. Rubinstein Ovalbumin increases macromolecular efflux from the in situ nasal mucosa of allergic hamsters J Appl Physiol, January 1, 1998; 84(1): 169 - 176. [Abstract] [Full Text] [PDF]

				X.-P. Gao Tannic acid elicits neurogenic plasma exudation from the in situ hamster cheek pouch Am J Physiol Regulatory Integrative Comp Physiol, January 1, 1998; 274(1): R237 - R242. [Abstract] [Full Text] [PDF]

				V. W.M. van Hinsbergh Endothelial Permeability for Macromolecules: Mechanistic Aspects of Pathophysiological Modulation Arterioscler. Thromb. Vasc. Biol., June 1, 1997; 17(6): 1018 - 1023. [Full Text]

				R. Draijer, D. E. Atsma, A. van der Laarse, and V. W.M. van Hinsbergh cGMP and Nitric Oxide Modulate Thrombin-Induced Endothelial Permeability : Regulation via Different Pathways in Human Aortic and Umbilical Vein Endothelial Cells Circ. Res., February 1, 1995; 76(2): 199 - 208. [Abstract] [Full Text]