Evidence that prostacyclin modulates the vascular actions of calcium in man.
Increases in extracellular calcium (Ca++) can alter vascular tone, and thus may result in increased blood pressure (Bp) and reduced renal blood flow (RBF). Ca++ can stimulate prostaglandin E2 (PGE2) and/or prostacyclin (PGI2) release in vitro, which may modulate Ca++ vascular effects. However, in man, the effect of Ca++ on PG release is not known. To study this, 14 volunteers received low-dose (2 mg/kg Ca++ gluconate) or high-dose (8 mg/kg) Ca++ infusions. The low-dose Ca++ infusion did not alter systemic or renal hemodynamics, but selectively stimulated PGI2, as reflected by the stable metabolite 6-keto-PGF1 alpha in urine (159 +/- 21-244 +/- 30 ng/g creatinine, P less than 0.02). The same Ca++ infusion given during cyclooxygenase blockade with indomethacin or ibuprofen was not associated with a rise in PGI2 and produced a rise in Bp and fall in RBF. However, sulindac, reported to be a weaker renal PG inhibitor, did not prevent the Ca++ -induced PGI2 stimulation (129 +/- 33-283 +/- 90, P less than 0.02), and RBF was maintained despite similar increases in Bp. The high-dose Ca++ infusion produced an increase in mean Bp without a change in cardiac output, and stimulated urinary 6-keto-PGF1 alpha to values greater than that produced by the 2-mg/kg Ca++ dose (330 +/- 45 vs. 244 +/- 30, P less than 0.05). In contrast, urinary PGE2 levels did not change. A Ca++ blocker, nifedipine, alone had no effect on Bp or urinary 6-keto-PGF1 alpha levels, but completely prevented the Ca++ -induced rise in Bp and 6-keto-PGF1 alpha excretion (158 +/- 30 vs. 182 +/- 38, P greater than 0.2). However, the rise in 6-keto-PGF1 alpha was not altered by the alpha 1 antagonist prazosin (159 +/- 21-258 +/- 23, P less than 0.02), suggesting that calcium entry and not alpha 1 receptor activation mediates Ca++ pressor and PGI2 stimulatory effects. These data indicate a new vascular regulatory system in which PGI2 modulates the systemic and renal vascular actions of calcium in man.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D015232:Dinoprostone; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D009318:Natriuresis / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D011224:Prazosin / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013467:Sulindac / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011458:Prostaglandins E; D013467:Sulindac; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D011464:Epoprostenol; D009543:Nifedipine; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium; D007052:Ibuprofen; D011224:Prazosin; D007213:Indomethacin