Journal of Applied Physiology, Vol 71, Issue 2 735-741, Copyright © 1991 by American Physiological Society

ARTICLES

In vivo attenuation of endothelium-dependent pulmonary vasodilation by methylene blue

J. R. Fineman, M. R. Crowley, M. A. Heymann and S. J. Soifer
Department of Pediatrics, University of California, San Francisco 94143.

In vitro evidence suggests that resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation are mediated by changes in vascular smooth muscle concentrations of guanosine 3',5'-cyclic monophosphate (cGMP). We investigated this hypothesis in vivo in 19 mechanically ventilated intact lambs by determining the hemodynamic effects of methylene blue (a guanylate cyclase inhibitor) and then by comparing the hemodynamic response to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimic) or methylene blue. Methylene blue caused a significant time-dependent increase in pulmonary arterial pressure. During U-46619 infusions, acetylcholine, ATP-MgCl2, sodium nitroprusside, isoproterenol, and 8-bromo-cGMP decreased pulmonary arterial pressure. During methylene blue infusions, the decreases in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) and sodium nitroprusside (an endothelium-independent guanylate cyclase-dependent vasodilator) were attenuated by greater than 50%. The decreases in pulmonary arterial pressure caused by isoproterenol and 8-bromo-cGMP (endothelium-independent vasodilators) were unchanged. This study in intact lambs supports the in vitro evidence that changes in vascular smooth muscle cell concentrations of cGMP in part mediate resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation.

This article has been cited by other articles:

				S. Wedgwood, J. M. Bekker, and S. M. Black Shear stress regulation of endothelial NOS in fetal pulmonary arterial endothelial cells involves PKC Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L490 - L498. [Abstract] [Full Text] [PDF]

				S. Kurotobi, T. Sano, S. Kogaki, T. Matsushita, T. Miwatani, M. Takeuchi, H. Matsuda, and S. Okada Bidirectional cavopulmonary shunt with right ventricular outflow patency: The impact of pulsatility on pulmonary endothelial function J. Thorac. Cardiovasc. Surg., June 1, 2001; 121(6): 1161 - 1168. [Abstract] [Full Text] [PDF]

				A. L. Hyman, Q. Hao, A. Tower, P. J. Kadowitz, H. C. Champion, B. Gumusel, and H. Lippton Novel catheterization technique for the in vivo measurement of pulmonary vascular responses in rats Am J Physiol Heart Circ Physiol, April 1, 1998; 274(4): H1218 - H1229. [Abstract] [Full Text] [PDF]

				W. Steudel, F. Ichinose, P. L. Huang, W. E. Hurford, R. C. Jones, J. A. Bevan, M. C. Fishman, and W. M. Zapol Pulmonary Vasoconstriction and Hypertension in Mice With Targeted Disruption of the Endothelial Nitric Oxide Synthase (NOS 3) Gene Circ. Res., July 19, 1997; 81(1): 34 - 41. [Abstract] [Full Text]

				C. J. Cooper, M. J. Landzberg, T. J. Anderson, F. Charbonneau, M. A. Creager, P. Ganz, and A. P. Selwyn Role of Nitric Oxide in the Local Regulation of Pulmonary Vascular Resistance in Humans Circulation, January 15, 1996; 93(2): 266 - 271. [Abstract] [Full Text]