Renal toxicity and arterial hypertension in rats chronically exposed to vanadate.

Abstract

The effects of 1, 10, or 40 juglml of vanadium, given for six or seven months as sodium metavanadate in drinking water on cardiovascular and biochemical variables and the electrolyte metabolism of male Sprague-Dawley rats were investigated. At the end of the exposure period, all animals exposed to vanadate had increased systolic and diastolic blood pressure. This effect was not dose dependent and heart rate and cardiac inotropism were not affected. The role of defective renal function and electrolyte metabolism in such effects was supported, in the rats exposed to 10 and 40 ppm of vanadium, by the following changes: (a) decreased Na,+ K+-ATPase activity in the distal tubules of nephrons; (b) increased urinary excretion of potassium; (c) increase in plasma renin activity and urinary kallikrein, kininase I, and kininase II activities; (d) increased plasma aldosterone (only in the rats treated with 10 ppm of vanadium). The alterations in the rats exposed to 1 ppm of vanadium were: (a) reduced urinary calcium excretion; (b) reduced urinary kallikrein activity; (c) reduced plasma aldosterone. These results suggest that blood hypertension in rats exposed to vanadate depends on specific mechanisms of renal toxicity related to the levels of exposure.

Acute Effects of Vanadate Oligomers on Heart, Kidney, and Liver Histology in the Lusitanian Toadfish (Halobatrachus didactylus)

“…However, several chronic studies, using rats that were forced to drink water with 100 ppm vanadium, have shown hypertension and/or augmented peripheral vascular resistance (Carmignani et al 1996). Further, male rats subjected to 1, 10, or 40 g/mL of sodium metavanadate in their drinking water also showed a dose-independent increase in systolic and diastolic blood pressures, while heart rate and cardiac inotropism were not affected (Boscolo et al 1994). These rats had diminished renal function, with alterations in the urinary excretion of electrolytes and in the activities of the kallikrein-kinin and the renin-angiotensin-aldosterone systems.…”

“…These include disorganization and hypochromia of renal tubule cell nuclei, picnotic lumen, and vacuolar areas in renal tubule cells, accumulation of amorphous eosinophilic material in the renal tubule nuclei, and reinforcement of reticular appearance in hepatocytes and leukocyte migration (Gutiérrez et al 1978;Establier and Gutiérrez 1980;Sarasquete et al 1982). Cardiovascular effects of heavy metals such as vanadium are also known, namely alterations of heart rate, cardiac inotropism, and peripheral vascular resistance (Boscolo et al 1994;Carmignani et al 1996), although histopathological effects in cardiac tissue are not completely understood.…”

Insulin and vanadate restore decreased plasma endothelin concentrations and exaggerated vascular responses to normal in the streptozotocin diabetic rat

“…While vanadium compounds represent an orally bioavailable insulinomimetic alternative with great potential for the treatment of Type I diabetes, they have well-established gastrointestinal, renal and cardiovascular toxicities per se [30,40,41]. Thus, despite the return to normal of ET action by insulin and vanadate treatment via correction of metabolic abnormalities, considerable limitations exist in the use of these agents in Type I diabetes.…”

Opinion of the Scientific Panel on Dietetic products, nutrition and allergies [NDA] related to the Tolerable Upper Intake Level of Vanadium

“…Such abnormalities were less evident in rats treated with 10 mg/L and absent in those treated with 1 mg/L of vanadium. At 10 and 40 mg/L, plasma renin, urinary kallikrein and urinary kininase I and II activities as well as urinary potassium were increased (Boscolo et al, 1994).…”