Magnesium influx enhanced by nitric oxide in hypertensive rat proximal tubule cells.
An abnormal handling of renal magnesium has been suggested to cause salt-sensitive hypertension. The filtered magnesium is first reabsorbed in the proximal tubule. Amiloride has been shown to enhance renal magnesium conservation, but the regulatory mechanisms are unknown yet. High-salt (8% NaCl) diet decreased serum magnesium concentration, while increased urinary magnesium in Dahl salt-sensitive (DS) rat. Furthermore, the expression of nitric oxide synthase type 3 and nitric oxide (NO) content were decreased in high-salt loaded DS rat. In isolated proximal tubule cells, amiloride (0.1 mM) increased intracellular free magnesium concentration ([Mg(2+)](i)). However, the net [Mg(2+)](i) increase in the high-salt loaded DS rat was smaller than other groups. NOR1 (0.1 mM), a NO donor, restored the increase of [Mg(2+)](i) to the same level of other groups. On the contrary, L-NMMA (0.1 mM), an inhibitor of NO production, inhibited the increase of [Mg(2+)](i) in all groups. These results suggest that intracellular NO has an important role to up-regulate amiloride-elicited magnesium influx.
Ikari
Akira
A
Department of Environmental Biochemistry and Toxicology, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Shizuoka 422-8526, Japan. ikari@u-shizuoka-ken.ac.jp
Kano
Tomoko
T
Suketa
Yasunobu
Y
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D020303:Rats, Inbred Dahl; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D008274:Magnesium