Role of extra- and intracellular Ca2+ in the lymphatic myogenic response.
We used an actively contracting in vitro preparation of bovine mesenteric lymph vessels to study the effect of selected calcium channel modulators on the ability of these vessels to propel fluid. We found that blocking the dihydropyridine receptor with nifedipine and diltiazem inhibited pumping at concentrations within the range used clinically (10(-7) and 10(-6) M, respectively). Intracellular calcium modulation using ryanodine (10(-6) M) also inhibited pumping. Furthermore, we studied the effect of these agents on the relationship between lymph flow and transmural pressure, a relationship normally described by a bell-shaped curve. Diltiazem, 10(-6) M, attenuated pumping over the range of pressures studied. On the other hand, ryanodine at 10(-7) M, a concentration capable of inhibiting pumping at a constant transmural pressure, had no effect on the pressure-flow relationship when transmural pressure was manipulated. Thus we have determined that calcium movement via the L-type channel contributes significantly to the regulation of lymph pump activity and that intracellular calcium flux plays a less significant role that may be modified by transmural pressure.
Atchison
D J
DJ
Sunnybrook Health Science Centre, Toronto, Canada.
Johnston
M G
MG
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020746:Calcium Channels, L-Type; D002417:Cattle; D004110:Diltiazem / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D008196:Lymph / Q000502:physiology; D008208:Lymphatic System / Q000187:drug effects / Q000502:physiology*; D008643:Mesentery; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D011312:Pressure; D012433:Ryanodine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D012433:Ryanodine; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium