Cadmium-induced Hypertension Research Articles

Inhibition of prostacyclin-like material formation by cadmium

The activity of cadmium on the platelet and vascular wall prostaglandin system was studied. This metal was found to inhibit the production of prostacyclin (PGI 2) by vascular wall tissue, without affecting the platelet aggregation induced by arachidonic acid or ADP. In view of the vasodilator activity of PGI 2 these data suggest an hypothesis on the origin of cadmium-induced hypertension and on the development of vascular thrombi.

The effects of cadmium on adrenergic neurotransmission [formula omitted][formula omitted

The effect of cadmium on the response of isolated perfused rabbit ear arteries to nerve stimulation and norepinephrine administration was examined. Cadmium in concentrations of .075–.25μM caused enhancement of the pressor responses to nerve stimulation, but higher concentrations caused inhibition of the response. The pressor response to norepinephrine was also inhibited by cadmium, but required a 100x higher concentration than that needed for inhibition of the response to nerve stimulation. The dual effect of cadmium on the response to nerve stimulation suggests a plausible explanation for the conflicting reports in the literature regarding the blood pressure effects of cadmium exposure. The enhancement by low concentrations of cadmium of the response to nerve stimulation provides a possible mechanism for cadmium-induced hypertension.

Genetic influence on cadmium-induced hypertension.

Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats were used to determine whether cadmium-induced hypertension is dependent on genetic predisposition. In experiment I, 16 wk-old R and S rats of both sexes were injected with two doses of cadmium (1 and 2 mg/kg body wt, ip), whereas the controls received the same volumes of saline. Hypertension and renal vascular changes were observed in cadmium-injected S rats but not in R rats. The S females appeared more sensitive than S males to the hypertensinogenic effect of cadmium. In experiment II, groups of weanling female R and S rats were given 0, 1, 2.5, 5, or 10 mg cadmium/liter drinking water and fed either a low-salt (0.4% NaCl) or a high-salt (4% NaCl) diet for 28 wk. Cadmium produced cardiac hypertrophy (1 mg cadmium/liter) and hypertension associated with renal vascular changes (1--5 mg cadmium/ liter), and it enhanced proteinuria (1-10 mg cadmium/liter) in S rats on a low-salt diet. Also, the development of salt-induced hypertension was accelerated in cadmium-fed (1 and 2.5 mg/liter) S rats. These adverse effects of cadmium were not detected in R rats on either salt diet. In experiments I and II, cadmium concentrations in the kidneys and liver of S rats were higher (P less than 0.001) than in those of R rats. These data indicate that genetic differences influence the pathogenesis of cadmium-induced hypertension.

A possible mechanism for cadmium-induced hypertension in rats

The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium in vitro was shown to inhibit both monoamine oxidase and catechol- O -methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. In vitro , cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.

A possible mechanism for cadmium-induced hypertension in rats

The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium in vitro was shown to inhibit both monoamine oxidase and catechol-O-methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. In vitro , cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.

Cadmium and zinc distribution in cardiovascular and other tissues of normal and cadmium-treated dogs

Cadmium, zinc and water concentrations in arterial segments from 11 different sites—heart, kidney cortex and medulla, liver, spleen, diaphragm, rib and sternum—of eight normal control and eight cadmium-treated dogs were compared. Cadmium treatment resulted in significant cadmium deposition in all of the tissues analyzed. Cardiovascular cadmium distribution in normal and treated dogs revealed higher cadmium levels in more peripheral and smaller arteries in comparison with the more central arteries and the myocardium. The distal mesenteric artery, mesenteric artery branches, main renal artery and coronary arteries tended to accumulate more cadmium in normal or cadmium-treated dogs or both. Zinc distribution in cardiovascular tissues revealed the highest zinc concentration in the mesenteric artery branches of normal dogs. Cadmium was, however, preferentially retained by the normal kidney and by the kidney and liver of cadmium-treated dogs. There were significant increases in zinc concentration of the kidney, liver and sternum in response to cadmium administration. Tissue cadmium/zinc ratio increased by a factor of 7.0–282.6 after cadmium administration. There were no significant alterations in the water content of the cadmium-treated tissues. The pathophysiological implications of these data in cadmium-induced hypertension are discussed.

Nervous Control of the Blood Vessels

Nervous Control of the Blood Vessels