Cadmium induces microcytosis and anisocytosis without anaemia in hypertensive rats.

Dietary cadmium (Cd2+) intake is implicated in the pathogenesis of hypertension and anaemia, but there is a paucity of information on the haematological changes in hypertensive conditions. This study, therefore, aims to evaluate the effects of Cd2+ on blood pressure (BP) and haematological indices in the Sprague-Dawley rat model. Three cohorts (n = 10 each) of control and Cd2+-fed male Sprague-Dawley rats were selected. Cd2+-exposed rats received 2.5 or 5 mg/kg b.w. cadmium chloride via gavage thrice-weekly for eight weeks, while control animals received tap water. BP and flow were measured non-invasively from rat tails twice-weekly using a CODA machine, while weights were measured thrice-weekly. Haematological indices were assessed using the Cell-Dyn Emerald Haematology Analyzer. Data were reported as mean ± SEM, and statistically analyzed using One-Way Analysis of Variance. Bonferroni post hoc test was used for multiple comparisons. Cd2+-exposure induced hypertension by significantly (p < 0.05) elevating systolic, diastolic, and mean arterial BPs, pulse pressure, and heart rate (HR), and increased (p < 0.05) blood flow. Mean cell volume (MCV) and haemoglobin (MCH) were significantly (p < 0.05) reduced, and red cell distribution width (RDW) significantly (p < 0.01) increased by exposure to 5 mg/kg b.w. Cd2+. Haemoglobin concentration (MCHC), haematocrit, haemoglobin, red blood cell, platelet, mean platelet volume, and white blood cell counts were unaffected by Cd2+-exposure. Cd2+ induced hypertension, microcytosis, hypochromicity, and anisocytosis without anaemia, which may be precursor to microcytic anaemia and coronary artery disease. This study is important in Cd2+-exposed environments and warrants further investigations.

Cadmium-induced hypertension is associated with renal myosin light chain phosphatase inhibition via increased T697 phosphorylation and p44 mitogen-activated protein kinase levels.

Dietary intake of the heavy metal cadmium (Cd2+) is implicated in hypertension, but potassium supplementation reportedly mitigates hypertension. This study aims to elucidate the hypertensive mechanism of Cd2+. Vascular reactivity and protein expression were assessed in Cd2+-exposed rats for 8 weeks to determine the calcium-handling effect of Cd2+ and the possible signaling pathways and mechanisms involved. Cd2+ induced hypertension in vivo by significantly (p < 0.001) elevating systolic blood pressure (160 ± 2 and 155 ± 1 vs 120 ± 1 mm Hg), diastolic blood pressure (119 ± 2 and 110 ± 1 vs 81 ± 1 mm Hg), and mean arterial pressure (133 ± 2 and 125 ± 1 vs 94 ± 1 mm Hg) (SBP, DBP, and MAP, respectively), while potassium supplementation protected against elevation of these parameters. The mechanism involved augmentation of the phosphorylation of renal myosin light chain phosphatase targeting subunit 1 (MYPT1) at threonine 697 (T697) (2.58 ± 0.36 vs 1 ± 0) and the expression of p44 mitogen-activated protein kinase (MAPK) (1.78 ± 0.20 vs 1 ± 0). While acetylcholine (ACh)-induced relaxation was unaffected, 5 mg/kg b.w. Cd2+ significantly (p < 0.001) attenuated phenylephrine (Phe)-induced contraction of the aorta, and 2.5 mg/kg b.w. Cd2+ significantly (p < 0.05) augmented sodium nitroprusside (SNP)-induced relaxation of the aorta. These results support the vital role of the kidney in regulating blood pressure changes after Cd2+ exposure, which may be a key drug target for hypertension management. Given the differential response to Cd2+, it is apparent that its hypertensive effects could be mediated by myosin light chain phosphatase (MLCP) inhibition via phosphorylation of renal MYPT1-T697 and p44 MAPK. Further investigation of small arteries and the Rho-kinase/MYPT1 interaction is recommended.

Apocynin ameliorates cadmium-induced hypertension through elevation of endothelium nitric oxide synthase.

Apocynin is reported to have antioxidant and NADPH oxidase inhibitor activities. Cadmium toxicity is reported to causes oxidative damage, resulting in vascular dysfunction, reduced bioavailability of nitric oxide (NO) and hypertension. The study aimed to investigate the protective effects of apocynin in cadmium-induced hypertension. Thirty-six (36) adult male Sprague-Dawley rats were randomly divided into 6 groups. Group 1 served as control, Groups 2 and 3 received 50 and 100 mg/Kg (b.w) apocynin, respectively, Group 4 received 100 ppm CdCl2 in their drinking water, while Group 5 and 6 received 100 ppm CdCl2 in their drinking and 50 and 100 mg/Kg (b.w) apocynin, respectively, for 8 weeks. Blood pressure readings were taken weekly using the tail-cuff method. cGMP, endothelial nitric oxide synthase (eNOS), NO and hematological parameters were analyzed at the end of 8 weeks. Apocynin, although a poor antioxidant, caused a significant reduction (p < 0.05) in systolic and mean arterial pressures in the cadmium-induced elevations in blood pressure and amelioration of altered hematological parameters. However, while cadmium exposures did not alter the cGMP, eNOS and nitrate concentrations in serum, apocynin reduced the cGMP and nitrite values while significantly elevating (p < 0.05) the eNOS concentrations and also improved the cadmium-induced anemia. Apocynin was effective in reducing cadmium-induced elevated blood pressures through elevation of eNOS. Inhibition of NADPH oxidase activity may be a useful strategy for prevention and treatment of cadmium-induced hypertension.