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HIGHLIGHTED TOPICS
Pulmonary Circulation and Hypoxia

Pressure-induced smooth muscle cell depolarization in pulmonary arteries from control and chronically hypoxic rats does not cause myogenic vasoconstriction

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

Submitted 2 August 2004 ; accepted in final form 28 September 2004

Chronic obstructive pulmonary diseases, as well as prolonged residence at high altitude, can result in generalized airway hypoxia, eliciting an increase in pulmonary vascular resistance. We hypothesized that a portion of the elevated pulmonary vascular resistance following chronic hypoxia (CH) is due to the development of myogenic tone. Isolated, pressurized small pulmonary arteries from control (barometric pressure 630 Torr) and CH (4 wk, barometric pressure = 380 Torr) rats were loaded with fura 2-AM and perfused with warm (37°C), aerated (21% O₂-6% CO₂-balance N₂) physiological saline solution. Vascular smooth muscle (VSM) intracellular Ca²⁺ concentration ([Ca²⁺]_i) and diameter responses to increasing intraluminal pressure were determined. Diameter and VSM cell [Ca²⁺]_i responses to KCl were also determined. In a separate set of experiments, VSM cell membrane potential responses to increasing luminal pressure were determined in arteries from control and CH rats. VSM cell membrane potential in arteries from CH animals was depolarized relative to control at each pressure step. VSM cells from both groups exhibited a further depolarization in response to step increases in intraluminal pressure. However, arteries from both control and CH rats distended passively to increasing intraluminal pressure, and VSM cell [Ca²⁺]_i was not affected. KCl elicited a dose-dependent vasoconstriction that was nearly identical between control and CH groups. Whereas KCl administration resulted in a dose-dependent increase in VSM cell [Ca²⁺]_i in arteries taken from control animals, this stimulus elicited only a slight increase in VSM cell [Ca²⁺]_i in arteries from CH animals. We conclude that the pulmonary circulation of the rat does not demonstrate pressure-induced vasoconstriction.

calcium; membrane potential; isolated vessels; chronic hypoxia

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