Published Online
on November 24, 2003

A more recent version of this article appeared on January 1, 2004

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Submitted on August 8, 2003
Revised on August 29, 2003

Low [Mg²⁺]_e Enhances Arterial Spontaneous Tone via Phosphatidylinositol 3-Kinase in DOCA-Salt Hypertension

Carrie A. Northcott^* and Stephanie W. Watts

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

^* To whom correspondence should be addressed. E-mail: taetscar{at}msu.edu.

Abstract--Phosphatidylinositol 3-kinase (PI3K) has been implicated in low extracellular Mg²⁺ concentration ([Mg²⁺]_e)-induced aortic contraction, and Mg²⁺ deficiency has been associated with hypertension. Moreover, arterial PI3K activity is increased in hypertensive deoxycorticosterone (DOCA)-salt rats. We hypothesized that low [Mg²⁺]_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 Mg²⁺ (0.15 mmol/L), high Mg²⁺ (4.8 mmol/L), or normal (1.17 mmol/L) physiologic salt solution (PSS) in isolated tissue baths. LY294002 (20 µmol/L), a PI3K inhibitor, or vehicle was added (30 minutes), followed by NE (10^-9 to 3x10^-5 mol/L). Low [Mg²⁺]_e significantly enhanced tone in aortas from DOCA-salt and sham rats compared with normal PSS (DOCA-salt low [Mg²⁺]_e, +51.5±7.0 vs DOCA-salt normal PSS, +7.1±1.4% of initial phenylephrine [PE] contraction). LY294002 and incubation with high Mg²⁺ PSS decreased tone in aortas from DOCA-salt rats (low [Mg²⁺]_e LY294002, -87.5±8.8; normal PSS LY294002, -81.7±13.7; and high [Mg²⁺]_e, -31.2±10.8% of initial PE contraction). Low [Mg²⁺]_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 [Mg²⁺]_e, -8.2±0.1; and DOCA-salt low [Mg²⁺]_e, -8.1±0.1). Moreover, this shift was inhibited by LY294002. In conclusion, low [Mg²⁺]_e might activate PI3K, leading to enhanced tone and agonist-induced contraction observed in aortas from DOCA-salt hypertensive rats.

Key words: magnesium • kinase • deoxycorticosterone • hypertension, sodium-dependent • phosphorylation

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