Physiologic increases in extracellular sodium salt enhance coronary vasoconstriction and Ca2+ entry

High dietary sodium salt has been suggested to increase the risk of coronary vasospasm and coronary artery disease. However, whether high-sodium salt directly affects the mechanisms of coronary artery contraction is unclear. This study investigated whether physiologic and supraphysiologic increases in extracellular concentrations of sodium chloride ([NaCl]e) enhance the Ca2+ handling mechanisms of coronary smooth muscle contraction. Isometric contraction and 45Ca2+ influx were measured in endothelium-denuded porcine coronary artery strips incubated in Krebs solution (2.5 mM Ca2+) containing increasing [NaCl]e (120, 121, 123, 126, 130, 140, and 150 mM). Increasing [NaCl]e for 30 min did not increase the resting coronary tone or 45Ca2+ influx. 5-Hydroxytryptamine (5-HT) caused concentration-dependent increases in contraction and 45Ca2+ influx. Preincubation of coronary strips in increasing [NaCl]e for 30 min did not change the median effective dose of 5-HT. However, the magnitude of the 5-HT contraction and 45Ca2+ influx was significantly increased at 121-126 mM [NaCl]e. Preincubation with 2,4-dichlorobenzamil (10-5 M), inhibitor of the Na+/Ca2+ exchanger, or KB-R7943 (10-5 M), selective inhibitor of the reverse mode of the Na+/Ca2+ exchanger, abolished the increases in 5-HT contraction and 45Ca2+ influx at 121-126 mM [NaCl]e. Preincubation in Krebs solution containing 120 mM NaCl plus 1-6 mM LiCl or N-methyl-d-glucamine did not increase 5-HT contraction or 45Ca2+ influx. Higher [NaCl]e (140-150 mM) increased 5-HT-induced 45Ca2+ influx but inhibited 5-HT contraction. 5-HT (10-5 M)- and caffeine (25 mM)-induced contraction in Ca2+-free (2 mM EGTA) solution, a measure of Ca2+ release from the intracellular stores, was not affected by small increases in [NaCl]e (121-126 mM) but was inhibited at higher [NaCl]e (130-150 mM). Thus increases in [NaCl]e within the physiologic range enhance coronary smooth muscle contraction to 5-HT by a mechanism possibly involving Ca2+ entry via the reverse mode of the Na+/Ca2+ exchanger, but not Ca2+ release from the intracellular stores. The reduction of coronary contraction with supraphysiologic [NaCl]e in both Ca2+-containing and Ca2+-free Krebs could be related to excessive increases in ionic strength and may mask significant coronary vasoconstrictor effects of physiologic increases in [NaCl]e.