Submitted to: Journal of Pharmacology
Publication Type: Proceedings
Publication Acceptance Date: 7/20/2001
Publication Date: 7/1/2002
Citation: Saari, J.T. 2002. Dietary copper deficiency reduces the elevation of blood pressure caused by nitric oxide synthase inhibition in rats. Pharmacology. 65:141-144.
Interpretive Summary: Nitric oxide is a chemical that is involved in the control of blood vessels. It is produced in blood vessels and causes increases in their diameter when its production is stimulated by any of a variety of hormones or nerves supplying the blood vessels. Prior studies have shown that the ability of nitric oxide to cause increases in blood vessel diameter is impaired when animals are fed copper-deficient diets. Because changes in blood vessel diameter have an important impact on blood pressure, this study was done to determine whether dietary copper deficiency, by an effect on nitric oxide, could affect control of blood pressure. Blood pressure was measured in anesthetized rats, half of which were copper-deficient, before and after injection of L-NAME, an inhibitor of the enzyme that produces nitric oxide. Blood pressure was not different between copper-adequate and copper-deficient rats before injection of L-NAME. However, after injection of L-NAME, blood pressure was elevated to a greater degree in copper-adequate than in copper-deficient rats. This indicates that nitric oxide has a greater influence in maintenance of resting blood pressure in copper-adequate than in copper-deficient rats. This is important to our understanding of the effect that dietary copper has on the heart and circulation.
Technical Abstract: Nitric oxide (NO)-mediated vasodilation is diminished in blood vessels of copper (Cu)-deficient rats. This study examined whether Cu deficiency affects blood pressure regulation via an effect on NO metabolism. Male, weanling rats were fed diets ranging from 0.4 to 7.2 mg Cu/kg diet for 5 wks. Blood pressure was measured via arterial cannulation before and after venous injection of L-NAME (10 mg/kg body wt), a NO synthase inhibitor. Plotting blood pressure against liver Cu concentration (22-241 nmol/g) revealed that control mean arterial blood pressure (MAP; 104-152 mm Hg) was not correlated with liver Cu concentration. However, both MAP after L-NAME treatment (MAPl, 148-190 mm Hg) and the elevation of MAP caused by L-NAME (delta MAP; 8-68 mm Hg) were positively correlated with liver Cu concentration (r=0.52 for MAPl; r=0.42 for delta MAP; p<0.05). This finding suggests that NO plays a significant role in maintaining basal blood pressure in Cu-adequate rats that is impaired by Cu deficiency.