Evidence for uneven distribution of L-type calcium channels in rat pulmonary circulation.

Experiments were performed on isolated, perfused rat lungs to determine the segmental sites of vasoconstriction in response to factors that open voltage-sensitive, L-type calcium channels on vascular smooth muscle cells. Lungs from male Sprague-Dawley rats were perfused at constant flow with a physiological saline solution (PSS) containing albumin. Measurements were made of pulmonary arterial and venous pressure, whereas capillary pressure was estimated by the double-occlusion technique. After equilibration, lungs were constricted with depolarizing PSS containing high K+ (35 or 45 mM). With both stimuli, approximately 80% of the observed increase in vascular resistance occurred on the arterial side of the circulation. Both nifedipine and verapamil reversed this response; however, reversal was more consistent in the arterial segment. In additional experiments, the L-type channel activator (-)BAY K 8644 caused increased resistance in the arterial but not the venous segment. Another group of lungs constricted with the thromboxane mimetic U-46619 demonstrated equal arterial and venous vasoconstriction. In U-46619-constricted lungs, nifedipine caused a 28% reversal of the agonist-induced increase in arterial resistance but was without effect on the venous circulation. These data suggest that a greater density of L-type calcium channels may exist within the arterial segment of the pulmonary circulation than in the veins.