AJP - Heart and Circulatory Physiology, Vol 249, Issue 4 741-H746, Copyright © 1985 by American Physiological Society

ARTICLES

BAY K 8644 potentiates and A23187 inhibits hypoxic vasoconstriction in rat lungs

I. F. McMurtry

The susceptibility of hypoxic pulmonary vasoconstriction to inhibition by Ca2+ channel antagonists suggests that membrane depolarization and Ca2+ influx are components of the hypoxic mechanism. Recent characterization of BAY K 8644 as a 1,4-dihydropyridine that facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels provides a new pharmacological tool to further test this idea. Effects of BAY K 8644 on normoxic vascular tone and on hypoxic and angiotensin II-induced vasoconstriction were examined in isolated rat lungs perfused with either blood or physiological salt solution (PSS) containing meclofenamate. Parallel experiments were performed with the Ca2+ ionophore A23187 for comparison with a Ca2+-active agent that does not act selectively on the voltage-dependent Ca2+ channel. Addition of BAY K 8644 (10(-7) to 10(-5) M) to the perfusate did not alter base-line vascular tone of the normoxic lung, but it potentiated hypoxic and angiotensin II pressor responses. For example, addition of 10(-7) M BAY K 8644 to five PSS-perfused lungs increased the hypoxic (5% O2) pressor response from 8.7 +/- 2.1 to 19.5 +/- 4.2 Torr and the angiotensin II (0.1 micrograms) response from 2.1 +/- 0.4 to 6.5 +/- 2.0 Torr. In contrast, addition of A23187 (10(-7) to 10(-6) M) to the perfusate increased normoxic perfusion pressure and inhibited hypoxic vasoconstriction. The respective effects of BAY K 8644 and A23187 were essentially the same in both blood- and PSS-perfused lungs. These results indicate that a Ca2+ channel facilitator and a Ca2+ ionophore have diametric effects on pulmonary vasoreactivity. The marked potentiation of hypoxic vasoconstriction by BAY K 8644 supports the idea that activation of voltage-dependent Ca2+ channels is an important component of the mechanism of hypoxic pulmonary vasoconstriction.

This article has been cited by other articles:

				R. Moudgil, E. D. Michelakis, and S. L. Archer Hypoxic pulmonary vasoconstriction J Appl Physiol, January 1, 2005; 98(1): 390 - 403. [Abstract] [Full Text] [PDF]

				Y. Morio and I. F. McMurtry Ca2+ release from ryanodine-sensitive store contributes to mechanism of hypoxic vasoconstriction in rat lungs J Appl Physiol, February 1, 2002; 92(2): 527 - 534. [Abstract] [Full Text] [PDF]

				J. X.-J. Yuan Oxygen-sensitive K+ channel(s): where and what? Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1345 - L1349. [Full Text] [PDF]

				E. A. Coppock, J. R. Martens, and M. M. Tamkun Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels Am J Physiol Lung Cell Mol Physiol, July 1, 2001; 281(1): L1 - L12. [Abstract] [Full Text] [PDF]

				Q. Liu, J. S. K. Sham, L. A. Shimoda, and J. T. Sylvester Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L856 - L865. [Abstract] [Full Text] [PDF]

				J. S. K. Sham, B. R. Crenshaw Jr., L.-H. Deng, L. A. Shimoda, and J. T. Sylvester Effects of hypoxia in porcine pulmonary arterial myocytes: roles of KV channel and endothelin-1 Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L262 - L272. [Abstract] [Full Text] [PDF]