Copper exposure for 30 days at a daily dose twice the recommended increases blood pressure and cardiac contractility

Copper is an essential factor for the body's homeostasis. However, excess copper compromises organic functions.

Aims: We investigated the effects of copper exposure for 30 days on blood pressure (BP) and cardiac contractility and the putative involvement of nitric oxide (NO) and reactive oxygen species.

Main methods: Wistar rats (12 weeks old, 280 g) were randomized to the treated group that was exposed for 30 days to copper (2000 μg/kg/day CuCl₂) and the control (Ct) group that received intraperitoneal saline (0.9%).

Key findings: The blood concentration of copper was ~1.26 μg/mL in the copper-exposed group and ~0.024 μg/mL in the Ct group. The main metal accumulations occurred in the liver and kidneys. Copper exposure increased systolic BP (Cu: 141 ± 3 mmHg; Ct: 133 ± 3 mmHg) (tail cuff method), left ventricular systolic pressure and papillary muscle force. Calcium release from the sarcoplasmic reticulum was reduced. The contractile response to Ca²⁺ was increased by copper, and the effect was not altered by L-NAME. Copper increased contractions dependent on sarcolemmal Ca²⁺ influx, and this effect was not altered by L-NAME. The percentage response to isoproterenol decreased in the copper-exposed group, but L-NAME did not alter this reduction. Papillary force development at the peak and plateau of tetanic contractions also increased after copper exposure, but this effect was not altered by L-NAME. In situ detection of OH local production increased.

Significance: Copper increased BP and cardiac force, increased Ca²⁺ inflow, reduced Ca²⁺ reuptake by the sarcoplasmic reticulum, and increased OH local production. Copper exposure at doses considered tolerable affects cardiac contractility.