Development of intrinsic tone in isolated pulmonary arterioles

In isolated porcine pulmonary arterioles with endothelium, intraluminal diameter measured at a transmural pressure of 20 mmHg decreased spontaneously from 233 ± 11 to 171 ± 12 μm in 135 min. This intrinsic constriction was not prevented by indomethacin, tetraethylammonium, or superoxide dismutase. Indomethacin plus N(G)-nitro-L-arginine methyl ester caused initial constriction and BQ-123 or BQ-123 plus BQ-788 caused initial dilation, but these treatments did not prevent subsequent progressive constriction. In pulmonary arterioles with endothelium exposed to calcium-free conditions and pulmonary arterioles without endothelium, the intraluminal diameter measured at a transmural pressure of 20 mmHg was constant at 239 ± 16 and 174 ± 7 μm, respectively. Thus the spontaneous development of tone in isolated pulmonary arterioles required extracellular calcium and resulted from 1) time-independent smooth muscle contraction caused by mechanisms intrinsic to smooth muscle and 2) time-dependent contraction caused by decreasing activity of endothelium-derived relaxing factors other than nitric oxide, vasodilator prostaglandins, and hyperpolarizing factors acting on calcium-dependent potassium channels or increasing activity of endothelium-derived contracting factors other than endothelin-1, vasoconstrictor prostaglandins, and superoxide anions. Further investigation is indicated to identify these unknown mechanisms and determine theft role in pulmonary vasoreactivity.