Low [Mg ]e Enhances Arterial Spontaneous Tone via Phosphatidylinositol 3-Kinase in DOCA-Salt Hypertension

Phosphatidylinositol 3-kinase (PI3K) has been implicated in low extracellular Mg concentration ([Mg ]e)– induced aortic contraction, and Mg deficiency has been associated with hypertension. Moreover, arterial PI3K activity is increased in hypertensive deoxycorticosterone (DOCA)-salt rats. We hypothesized that low [Mg ]e activates PI3K, eliciting enhanced vascular contraction, PI3K activity, and norepinephrine (NE)-induced contraction. Spontaneous tone was monitored in endothelium-denuded aortic strips from sham and DOCA-salt rats exposed to low Mg (0.15 mmol/L), high Mg (4.8 mmol/L), or normal (1.17 mmol/L) physiologic salt solution (PSS) in isolated tissue baths. LY294002 (20 mol/L), a PI3K inhibitor, or vehicle was added (30 minutes), followed by NE (10 9 to 3 10 5 mol/L). Low [Mg ]e significantly enhanced tone in aortas from DOCA-salt and sham rats compared with normal PSS (DOCA-salt low [Mg ]e, 51.5 7.0 vs DOCA-salt normal PSS, 7.1 1.4% of initial phenylephrine [PE] contraction). LY294002 and incubation with high Mg PSS decreased tone in aortas from DOCA-salt rats (low [Mg ]e LY294002, 87.5 8.8; normal PSS LY294002, 81.7 13.7; and high [Mg ]e, 31.2 10.8% of initial PE contraction). Low [Mg ]e leftward-shifted NE-induced aortic contractions in sham and thus matched the shift observed with DOCA ( log EC50 mol/L: sham PSS, 7.7 0.1; DOCA-salt PSS, 8.2 0.1; sham low [Mg 2 ]e, 8.2 0.1; and DOCA-salt low [Mg ]e, 8.1 0.1). Moreover, this shift was inhibited by LY294002. In conclusion, low [Mg 2 ]e might activate PI3K, leading to enhanced tone and agonist-induced contraction observed in aortas from DOCA-salt hypertensive rats. (Hypertension. 2004;43:125-130.)