E. Kenneth Weir

The Pulmonary Circulation in Health and Disease

Control of blood flow through the pulmonary circulation is unique for several reasons. Unlike other organs, the lungs must accept the entire cardiac output. Despite receiving the entire cardiac output, pulmonary artery pressure must remain low to allow the exchange of oxygen and carbon dioxide across the thin layer of cells separating the capillaries and the alveoli. The maintenance of this low pressure circulation is dependent upon the metabolically active pulmonary vascular endothelium and the production of vasoactive mediators. Endothelial dysfunction can result in alterations in pulmonary vascular tone, pulmonary hypertension, or alterations in vascular permeability, pulmonary edema. The critical role of the endothelium in the maintenance of vascular tone and integrity will be discussed in this chapter.

K+ Channels and the Normoxic Constriction of the Rabbit Ductus Arteriosus

The ductus arteriosus (DA) is a vital fetal structure that acts as a right-to-left shunt to divert blood flow away from the constricted pulmonary circulation in the developing fetus. At birth, the DA constricts as a direct result of the increase in oxygen (O2) tension that occurs. The mechanism for this O2-mediated constriction remains controversial. We have shown that the smooth muscle of the DA contains at least two types of potassium (K+) channel, a 4-aminopyridine-sensitive, delayed rectifier (Kv) channel and a tetraethlyammonium-sensitive, calcium- (Ca2+-) dependent K+ channel. Increased levels of O2 appear to selectively inhibit the activity of the Kv channel. Because this channel controls the resting membrane potential of DA smooth muscle cells, this inhibition results in the depolarization of the cell membrane, opening of voltage-gated L-type Ca2+ channels, influx of Ca2+, and hence constriction. We suggest that, under normal conditions, this mechanism may initiate the normoxic constriction of the DA.