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 mu g/kg/day CuCl2) and the control (Ct) group that received intraperitoneal saline (0.9%). Key findings: The blood concentration of copper was ~1.26 mu g/mL in the copper-exposed group and ~0.024 mu g/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 & BULL; local production increased. Significance: Copper increased BP and cardiac force, increased Ca2+ inflow, reduced Ca2+ reuptake by the sarcoplasmic reticulum, and increased OH center dot local production. Copper exposure at doses considered tolerable affects cardiac contractility.

Automated summary

Excessive copper exposure increases blood pressure and cardiac force, enhances Ca2+ inflow, reduces Ca2+ reuptake by the sarcoplasmic reticulum, and increases the production of hydroxyl radicals locally.