Development of intrinsic tone in isolated pulmonary arterioles

In isolated porcine pulmonary arterioles with endothelium, intraluminal dia meter measured at a transmural pressure of 20 mmHg decreased spontaneously from 233 +/- 11 to 171 +/- 12 mu m in 135 min. This intrinsic constriction was not prevented by indomethacin, tetraethylammonium, or superoxide dismut ase. Indomethacin plus N-G-nitro-L-arginine methyl ester caused initial con striction and BQ-123 or BQ-123 plus BQ-788 caused initial dilation, but the se treatments did not prevent subsequent progressive constriction. In pulmo nary arterioles with endothelium exposed to calcium-free conditions and pul monary arterioles without endothelium, the intraluminal diameter measured a t a transmural pressure of 20 mmHg was constant at 239 +/- 16 and 174 +/- 7 mu m, respectively. Thus the spontaneous development of tone in isolated p ulmonary arterioles required extracellular calcium and resulted from 1) tim e-independent smooth muscle contraction caused by mechanisms intrinsic to s mooth muscle and 2) time-dependent contraction caused by decreasing activit y of endothelium-derived relaxing factors other than nitric oxide, vasodila tor prostaglandins, and hyperpolarizing factors acting on calcium-dependent potassium channels or increasing activity of endothelium-derived contracti ng factors other than endothelin-1, vasoconstrictor prostaglandins, and sup eroxide anions. Further investigation is indicated to identify these unknow n mechanisms and determine their role in pulmonary vasoreactivity.