Renal function of cyclin M2 Mg2+ transporter maintains blood pressure.

Abstract

Epidemiological studies have shown that magnesium intake/excretion is inversely correlated with blood pressure (BP), and artificial supplementation of magnesium was able to prevent hypertension. However, there has been no molecular genetic study showing the importance of magnesium homeostasis in BP regulation. We analyzed magnesium content and BP of mice lacking genes encoding cyclin M (CNNM) Mg transporter family proteins. Systemic heterozygotes and the kidney-specific homozygotes for Cnnm2-deficient alleles are both viable and show hypomagnesemia, indicating the important function of CNNM2 in maintaining magnesium homeostasis in the kidney. Endogenous CNNM2 localizes at the basolateral membrane of kidney distal convoluted tubule cells, which play important roles not only in magnesium reabsorption but also in BP control. The BP of these viable strains is significantly reduced; the SBP values by telemetric measurements are 121.7 ± 2.8 mmHg in wild-type, and 110.2 ± 2.7 and 109.7 ± 3.6 mmHg in systemic heterozygotes and kidney-specific homozygotes, respectively. Analyses of mice lacking CNNM Mg transporters clearly demonstrated abnormalities in BP values, confirming the importance of magnesium homeostasis in maintaining BP.