Short-term Effects of Cadmium Exposure on Blood Pressure and Vascular Function in Wistar Rats.

Chronic cadmium exposure is known to be associated with vascular changes and increased blood pressure, but its short-term effects on the cardiovascular system remain poorly understood. This study aimed to investigate the pressoric and vascular effects of a 7-day exposure to CdCl2 in Wistar rats. The rats were divided in control group (Ct), which received tap water, and the Cd group, which received a 100 mg/L CdCl2 solution via drinking water for 7 days. We analyzed body weight, plasma Cadmium concentration, systolic blood pressure (SBP), and vascular responses. Despite relatively low plasma Cadmium concentration, the Cd group exhibited elevated SBP and increased contractile response to phenylephrine. Endothelium removal and NOS inhibition increased contractions in both groups. In the Cd group's aorta, we observed enhanced levels of phospho-eNOS (Ser1177) and basal NO release. Cd group showed reduced Catalase expression and increased basal release of H2O2, with catalase reducing the contractile response. In arteries pre-contracted with phenylephrine, Cd group showed impaired endothelium-dependent (Acetylcholine) and independent (sodium nitroprussiate-SNP) relaxation responses. However, responses to SNP were similar after pre-contraction with KCl in both groups. These data suggest early effects of Cadmium on blood pressure and aortic function, indicating impaired H2O2-scavenging by catalase. Increased H2O2 due to Cadmium exposure might explain heightened responses to phenylephrine and weakened relaxation responses mediated by the NO-K+-channels pathway. Our findings shed light on Cadmium's short-term impact on the cardiovascular system, providing insights into potential mechanisms underlying its effects on blood pressure regulation and vascular function.

In vitro cadmium exposure induces structural damage and endothelial dysfunction in female rat aorta.

Cadmium is a heavy metal that is widespread in the environment and has been described as a metalloestrogen and a cardiovascular risk factor. Experimental studies conducted in male animals have shown that cadmium exposure induces vascular dysfunction, which could lead to vasculopathies caused by this metal. However, it is necessary to investigate the vascular effects of cadmium in female rats to understand its potential sex-dependent impact on the cardiovascular system. While its effects on male rats have been studied, cadmium may act differently in females due to its potential as a metalloestrogen. In vitro studies conducted in a controlled environment allow for a direct assessment of cadmium's impact on vascular function, and the use of female rats ensures that sex-dependent effects are evaluated. Therefore, the aim of this study was to investigate the in vitro effects of Cadmium Chloride (CdCl2, 5 µM) exposure on vascular reactivity in the isolated aorta of female Wistar rats. Exposure to CdCl2 damaged the architecture of the vascular endothelium. CdCl2 incubation increased the production and release of O2•-, reduced the participation of potassium (K+) channels, and increased the participation of the angiotensin II pathway in response to phenylephrine. Moreover, estrogen receptors alpha (Erα) modulated vascular reactivity to phenylephrine in the presence of cadmium, supporting the hypothesis that cadmium could act as a metalloestrogen. Our results demonstrated that in vitro cadmium exposure induces damage to endothelial architecture and an increase in oxidative stress in the isolated aorta of female rats, which could precipitate vasculopathies. Graphical Abstract. Own source from Canva and Servier Medical Art servers.

Long-term Mercury Exposure Accelerates the Development of Hypertension in Prehypertensive Spontaneously Hypertensive Rats Inducing Endothelial Dysfunction: the Role of Oxidative Stress and Cyclooxygenase-2.

Mercury is a metal widely dispersed in nature that when in contact with human organism, it damages the cardiovascular system. Long-term mercury exposure for 30 days induces endothelial dysfunction without blood pressure changes in normotensive adult rats. However, it is not known whether exposure to mercury can exacerbate endothelial dysfunction and hypertension development in predisposed animals. Thus, we aimed to investigate the effects of long-term mercury exposure on the blood pressure (BP) and in the isolated aortas of young normotensive and prehypertensive spontaneously hypertensive rats (SHRs). Four-week-old male Wistar rats and SHRs were treated daily with mercury chloride (HgCl2) (1st dose, 4.6 µg/kg; subsequent dose, 0.07 µg/kg/day, im, 30 days) or vehicle. BP was assessed weekly and the vascular reactivity to phenylephrine was evaluated in isolated aorta from rats exposed or not to mercury. Mercury exposure did not affect BP in young Wistar rats but accelerated the development of hypertension in young SHRs. Vascular reactivity to phenylephrine increased only in the aorta from mercury-exposed SHRs. While HgCl2 exposure in SHRs did not alter nitric oxide production, we observed increased superoxide anion production and decreased superoxide dismutase-1 protein expression, and enhanced cyclooxygenase-2 (COX-2) participation with increased prostaglandin (PGE2) production and decreased prostacyclin. In the Wistar group, mercury exposure did not alter superoxide anion production or the COX-2 pathway. Mercury exposure accelerated the natural course of hypertension in young SHRs and increased oxidative stress associated with reduced participation of antioxidant enzymes, an activated COX-2 pathway, thereby producing endothelial dysfunction, which is a risk factor in prehypertensive individuals.