Journal of Applied Physiology, Vol 80, Issue 1 91-98, Copyright © 1996 by American Physiological Society

ARTICLES

Pulmonary vasoreactivity to endothelin-1 at elevated vascular tone is modulated by potassium channels

S. A. Barman
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, USA.

The role of K+ channels on the pressor effect of endothelin-1 (ET-1) on vascular resistance and compliance in the canine pulmonary circulation was studied by using three different K+ channel inhibitors in isolated blood-perfused dog lungs when vascular tone was elevated with U-46619: 1) 10(-6) M glibenclamide, a potent and selective blocker of ATP-sensitive K+ channels; 2) 1 mM tetraethylammonium ions (TEA), an inhibitor of Ca(2+)-dependent K+ channels; and 3) 10(-4) M 4-aminopyridine, a nonspecific inhibitor of K+ channels. The results of the present study showed that under control vascular tone, 10(-8) M ET-1 increased total vascular resistance and capillary pressure by increasing postcapillary resistance. In addition, ET-1 decreased total vascular compliance. When vascular tone was elevated, ET-1 elicited an initial transient vasodilation followed by a sustained mild vasoconstriction that was lesser in magnitude than that observed under normal vascular tone. In addition, the increases in postcapillary resistance and capillary pressure and the decrease in vascular compliance that was observed with ET-1 at normal vascular tone was not present. Pretreatment with glibenclamide, TEA, and 4-aminopyridine at elevated vascular tone significantly potentiated the pressor effect of ET-1, and TEA blocked the transient vasodilation to ET-1. These data indicate that when pulmonary vasomotor tone is elevated with U-46619, Ca(2+)-dependent K+ channels may play a significant role in mediating the vasodilator response to ET-1 while ATP-sensitive, Ca(2+)-dependent, and other voltage-activated K+ channels attenuate the pulmonary vasoconstrictor response to ET-1.

This article has been cited by other articles:

				S. A. Barman Vasoconstrictor effect of endothelin-1 on hypertensive pulmonary arterial smooth muscle involves Rho-kinase and protein kinase C Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L472 - L479. [Abstract] [Full Text] [PDF]

				O. Platoshyn, C. V. Remillard, I. Fantozzi, M. Mandegar, T. T. Sison, S. Zhang, E. Burg, and J. X.-J. Yuan Diversity of voltage-dependent K+ channels in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L226 - L238. [Abstract] [Full Text] [PDF]

				J. A. Madden Focus on "Hypoxic constriction of porcine distal pulmonary arteries: endothelium and endothelin dependence" Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L853 - L855. [Full Text] [PDF]

				S. A. Barman Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction Am J Physiol Lung Cell Mol Physiol, May 1, 2001; 280(5): L888 - L895. [Abstract] [Full Text] [PDF]

				S. A. Barman Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation Am J Physiol Lung Cell Mol Physiol, September 1, 1999; 277(3): L558 - L565. [Abstract] [Full Text] [PDF]

				A. M. Evans, O. N. Osipenko, S. G. Haworth, and A. M. Gurney Resting potentials and potassium currents during development of pulmonary artery smooth muscle cells Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H887 - H899. [Abstract] [Full Text] [PDF]

				S. A. Barman Potassium channels modulate hypoxic pulmonary vasoconstriction Am J Physiol Lung Cell Mol Physiol, July 1, 1998; 275(1): L64 - L70. [Abstract] [Full Text] [PDF]

				S. A. Barman Pulmonary vasoreactivity to serotonin during hypoxia is modulated by ATP-sensitive potassium channels J Appl Physiol, August 1, 1997; 83(2): 569 - 574. [Abstract] [Full Text] [PDF]