Effects of intravenous magnesium infusion on in vivo release of acetylcholine and catecholamine in rat adrenal medulla.

We applied microdialysis technique to the left adrenal medulla of anesthetized rats and examined the effects of intravenous Mg(2+) infusion on presynaptic acetylcholine (ACh) release and postsynaptic catecholamine release induced by electrical stimulation of splanchnic nerves. The dialysis probes were perfused with Ringer's solution containing neostigmine. Low-dose MgSO4 (25 µmol/kg/min for 30 min i.v.) increased mean plasma Mg(2+) concentration to 2.5mM; the administration suppressed norepinephrine (NE) release by approximately 30% and epinephrine (Epi) release by approximately 20%, but did not affect ACh release. High-dose MgSO4 (50 µmol/kg/min for 30 min i.v.) increased mean plasma Mg(2+) concentration to 3.8mM; the administration suppressed ACh release by approximately 25%, NE release by approximately 60% and Epi release by approximately 45%. Administration of Na2SO4 (50 µmol/kg/min for 30 min i.v.) did not change the release of ACh, NE or Epi. Local administration of nifedipine (200 µM) suppressed NE release by approximately 40% and Epi release by approximately 30%, but did not affect ACh release. In the presence of nifedipine, low-dose MgSO4 did not suppress the release of ACh, or further suppress NE or Epi compared to nifedipine alone, but high-dose MgSO4 suppressed ACh release by approximately 25% and further suppressed NE release by approximately 60% and Epi release by approximately 50% compared to nifedipine alone. In conclusion, intravenous administration of Mg(2+) inhibits both presynaptic ACh release and postsynaptic catecholamine release in the adrenal medulla, but L-type Ca(2+) channel-controlled catecholamine release may be more sensitive to Mg(2+) than non-L-type Ca(2+) channel-controlled ACh release.

Vagal stimulation suppresses ischemia-induced myocardial interstitial myoglobin release.

AIMS: To evaluate vagal stimulation-mediated myocardial protection against ischemia and reperfusion in in vivo ischemic myocardium. MAIN METHODS: We measured myocardial interstitial myoglobin levels in the ischemic region using a cardiac microdialysis technique in anesthetized and vagotomized cats. We occluded the left anterior descending coronary artery (LAD) for 60 min and reperfused it for 60 min (VX group, n = 6). The effects of bilateral vagal stimulation (10 V, 5 Hz, 1-ms pulse duration), initiated immediately after LAD occlusion, were examined (VS group, n = 6). To examine the involvement of phosphatidylinositol 3-kinase (PI3K), vagal stimulation was performed after pretreatment with a PI3K inhibitor wortmannin (0.6 mg/kg, i.v.) (VS-W group, n = 6). To examine the contribution of bradycardia, vagal stimulation was performed with fixed-rate ventricular pacing (VS-P group, n = 6). KEY FINDINGS: The average myoglobin level during the ischemic period was 1170+/-141 in VX (in ng/ml, mean+/-SE), which was significantly attenuated in VS (466+/-87, P<0.05) and VS-W (613+/-124, P<0.05) but not in VS-P (953+/-203). Reperfusion increased the myoglobin level to 2500+/-544 in VX, whereas it was suppressed in VS (824+/-213, P<0.05) and VS-W (948+/-315, P<0.05) but not in VS-P (1710+/-253). SIGNIFICANCE: Vagal stimulation, initiated immediately after LAD occlusion, attenuated the myocardial injury. Moreover, bradycardia, independent of PI3K pathway, plays a significant role in vagally induced cardioprotection during acute myocardial ischemia.