HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/L797    most recent 00253.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Broughton, B. R. S. Articles by Resta, T. C. PubMed PubMed Citation Articles by Broughton, B. R. S. Articles by Resta, T. C.

Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries

Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico

Submitted 1 July 2007 ; accepted in final form 4 February 2008

Myogenic tone in the pulmonary vasculature of normoxic adult animals is minimal or nonexistent. Whereas chronic hypoxia (CH) increases basal tone in pulmonary arteries, it is unclear if a portion of this elevated tone is due to development of myogenicity. Since basal arterial RhoA activity and Rho kinase (ROK) expression are augmented by CH, we hypothesized that CH elicits myogenic reactivity in pulmonary arteries through ROK-dependent vascular smooth muscle (VSM) Ca²⁺ sensitization. To test this hypothesis, we assessed the contribution of ROK to basal tone and pressure-induced vasoconstriction in endothelium-disrupted pulmonary arteries [50–300 µm inner diameter (ID)] from control and CH [4 wk at 0.5 atmosphere (atm)] rats. Arteries were loaded with fura-2 AM to continuously monitor VSM intracellular Ca²⁺ concentration ([Ca²⁺]_i). Basal VSM [Ca²⁺]_i was not different between groups. The ROK inhibitor, HA-1077 (100 nM to 30 µM), caused a concentration-dependent reduction of basal tone in CH arteries but had no effect in control vessels. In contrast, PKC inhibition with GF109203X (1 µM) did not alter basal tone. Furthermore, significant vasoconstriction in response to stepwise increases in intraluminal pressure (5–45 mmHg) was observed at 12, 15, 25, and 35 mmHg in arteries (50–200 µm ID) from CH rats. This myogenic reactivity was abolished by HA-1077 (10 µM) but not by GF109203X. VSM [Ca²⁺]_i was unaltered by HA-1077, GF109203X, or increases in pressure in either group. Myogenicity was not observed in larger vessels (200–300 µm ID). We conclude that CH induces myogenic tone in small pulmonary arteries through ROK-dependent myofilament Ca²⁺ sensitization.

pulmonary hypertension; protein kinase C; vascular smooth muscle; Ca²⁺ sensitization; HA-1077

This article has been cited by other articles:

				N. L. Jernigan, B. R. Walker, and T. C. Resta Reactive oxygen species mediate RhoA/Rho kinase-induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L515 - L529. [Abstract] [Full Text] [PDF]

				G. A. Knock, V. A. Snetkov, Y. Shaifta, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery Cardiovasc Res, August 23, 2008; (2008) cvn209v2. [Abstract] [Full Text] [PDF]