Enhanced vascular reactivity and Ca2+ entry with low-salt diet: effect of obesity

Salt moderation is often recommended as a nonpharmacological therapy for hypertension, particularly in overweight individuals; however, the effects of low dietary salt on the Ca(2+)-dependent mechanisms of vasoconstriction are unclear. The purpose of this study was to investigate the effect of low salt diet on vascular reactivity and Ca2+ mobilization mechanisms and the modulation of these effects with obesity. Active stress and (45)Ca2+ influx were measured in deendothelialized aortic strips isolated from lean (3.74 kg) and obese (5.51 kg) female rabbits on a normal (0.75%) or low (0.23%) salt (sodium chloride) diet for 18 weeks. Both phenylephrine (Phe, 10(-5) mol/L) and membrane depolarization by 96 mmol/L KCl caused extracellular Ca(2+)-dependent increases in active stress and (45)Ca2+ influx. In lean rabbits, the Phe- and KCl-induced stress and Ca2+ influx were significantly greater with the low-salt versus the normal-salt diet. The Phe-induced Ca2+ influx-stress relationship was significantly greater than that induced by KCl with low-salt diet. In obese rabbits on a normal-salt diet, the Phe- and KCl-induced stress and Ca2+ influx were significantly less than that in lean rabbits but the Ca2+ influx-stress relationship was not significantly altered. Feeding the obese rabbits a low-salt diet was associated not only with significant increases in Phe- and KCl-induced active stress and Ca2+ influx but also with significant enhancement in the Ca2+ influx-stress relationship. In Ca(2+)-free (2 mmol/L EGTA) Krebs solution, stimulation of intracellular Ca2+ release by Phe or caffeine (25 mmol/L) caused a transient contraction that was not significantly different in all groups of rabbits. Thus, with normal salt intake, obesity is associated with a reduction in Ca2+ entry and vascular reactivity. Low-salt diet is associated with an increase in Ca2+ entry and vascular reactivity in both obese and lean rabbits. The enhancement of the Ca2+ influx-stress relationship with low-salt diet, particularly in the obese rabbits, suggests activation of other contractile mechanisms in addition to Ca2+ entry.