Evidence That Prostacyclin Mediates the Vascular Action of Magnesium in Humans

Evidence in vitro and in humans suggests that Mg can alter systemic and renal vascular tone. However, the mechanism of these effects is not known. The role of vasodilator prostaglandin release and Ca flux in Mg-induced changes in blood pressure and renal blood flow was studied in 10 normal subjects maintained on a fixed 80-mEq Na and K diet. Magnesium sulfate infused at 200 mg/hr for 3 hours reduced systolic and diastolic blood pressure within 1 hour (from 119 ± 2 [SEM] to 109 ± 4 mm Hg systolic; from 74 ± 3 to 64 ± 4 mm Hg diastolic; p < 0.02). This hypotensive response was seen in all subjects and persisted for 3 hours. The pulse rate did not change, but renal blood flow (p-aminohippurate clearance) increased (from 902 ± 78 to 1108 ± 130 ml/min/1.73 m; p < 0.05). The Mg infusion produced a significant increase in the excretion of the stable prostaglandin I2 (PGIj) metabolite 6-keto-PGFla (from 96 ± 12 to 154 ± 16 ng/g creatinine; p < 0.01). In contrast, urinary PGEj was not altered (328 ± 75 vs 399 ± 145 ng/g creatinine; p > 0.6). To evaluate the functional role of PGIj release, the cyclooxygenase inhibitors indomethacin (75 mg) or ibuprofen (600 mg) were given before the Mg+ infusion. Both cyclooxygenase blockers, given in doses that inhibited immunoreactive 6-keto-PGF, a release, completely prevented the Mg-induced decline in blood pressure and increased renal blood flow. In addition, pretreatment with the Ca channel antagonist nifedipine (20 mg sublingual) blocked the Mg-stimulated rise in PGI2 and fall in blood pressure. These results suggest that Ca flux and PGI2 release play a role in mediating the vascular action of MgJ+ in humans.