Abstract
Recently we demonstrated a principal role of nitric oxide (NO) in the endothelium/shear‐dependent regulation of contractility in thoracic duct (TD). We tested the hypothesis that cGMP/PKG is involved in the intrinsic & extrinsic flow‐dependent modulation of lymphatic contractility. Diameters & indices of lymphatic pumping of isolated, cannulated & pressurized segments of rat TD were measured. The influences of incrementally increased transmural pressure (1 to 5 cm H2O) and imposed flow (1 to 5 cm H2O transaxial pressure gradient) were examined before & after treatment with cGMP analog and antagonist. We found that the cGMP analog ‐ 8pCPTcGMP (1‐100 µM) mimics the extrinsic flow‐induced relaxation in a dose‐dependent manner. Treatment of TD by the cGMP/PKG inhibitor ‐ Rp‐8‐Br‐PET‐cGMPS (10‐50 µM) eliminated the NO‐dependent intrinsic flow‐dependent relaxation, and largely prevented the extrinsic flow‐dependent relaxation. Western blotting demonstrated the presence of both PKGα and β isoforms in TD, with ~10‐times greater expression of the PKGα protein in TD compared with aorta and vena cava. The PKGβ isoform expressed equally in TD and vena cava, both being ~2 times higher than that in the aorta. These findings demonstrate that cGMP is critical to the flow‐dependent regulation of TD contractility; and also suggests important involvement of PKG in these processes. NIH HL70308
Published Version
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