Arsenic exposure decreases rhythmic contractions of vascular tone through sodium transporters and K+ channels

Abstract

Arsenic-contaminated drinking water is a public health problem in countries such as Taiwan, Bangladesh, United States, Mexico, Argentina, and Chile. The chronic ingestion of arsenic-contaminated drinking water increases the risk for ischemic heart disease, cerebrovascular disease, and prevalence of hypertension. Although toxic arsenic effects are controversial, there is evidence that a high concentration of arsenic may induce hypertension through increase in vascular tone and resistance. Vascular tone is regulated by the rhythmic contractions of the blood vessels, generated by calcium oscillations in the cytosol of vascular smooth muscle cells. To regulate the cytosolic calcium oscillations, the membrane oscillator model involves the participation of Ca²⁺ channels, calcium-activated K⁺ channels, Na⁺/Ca²⁺ exchange, plasma membrane Ca²⁺-ATPase, and the Na⁺/K⁺-ATPase. However, little is known about the role of K⁺ uptake by sodium transporters [Na⁺/K⁺-ATPase or Na⁺-K⁺-2Cl^- (NKCC1)] on the rhythmic contractions. Vascular rhythmic contractions, or vasomotion are a local mechanism to regulate vascular resistance and blood flow. Since vascular rhythmic contractions of blood vessels are involved in modulating the vascular resistance, the blood flow, and the systemic pressure, we suggest a model explaining the participation of the sodium pump and NKCC1 co-transporter in low dose arsenic exposure effects on vasomotion and vascular dysfunction.

Keywords: Arsenic, Vasomotion, Na⁺/K⁺-ATPase, Na⁺-K⁺-2Cl^-, K⁺ channels, Nitric oxide, Prostaglandin, Vascular

Core tip: Vascular tone is regulated in part by cytosolic calcium oscillations. Arsenic can induce an increase in vascular tone and resistance. We suggest a model explaining the participation of the sodium pump and Na⁺-K⁺-2Cl^- co-transporter in low dose arsenic exposure effects on vasomotion and vascular dysfunction.