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.
Male weanling Wistar rats received 200 pg/mi of mercury (Hg), as HgCl,, in drinking water for 180 days. At the end of the treatment, systemic arterial blood pressure was augmented, cardiac inotropism was reduced, and heart rate was unchanged. Light and electron microscopical studies of the kidney showed a mesangial proliferative glomerulonephritis in about 80% of the glomeruli. Tubular cells showed reduction of the acid phosphatase activity, which was related to functional abnormalities of the lysosomes. In the 24 hour urine samples ofthe Hg exposed rats, there was slight reduction of kallikrein activity, but evident proteinuria was not present in all samples. Plasma renin activity was reduced, that of angiotensin I-converting enzyme was augmented, and plasma aldosterone concentrations were unchanged. Mercury was accumulated mostly in the kidney of the Hg treated animals; and the content of Hg in the heart was higher than in the brain. These data show that chronic exposure to Hg acts on the kidney with complex mechanisms of toxicity; these contribute to modify systemic haemodynamics. The purpose of this study was to investigate some mechanisms of renal toxicity possibly involved in the dysfunction of cardiovascular function, in rats exposed to doses of Hg known to induce both arterial hypertension and autoimmune lesions in the kidney. Materials and methodsSixteen male weanling Wistar rats were randomly divided into two equal groups, housed in stainless steel cages, and fed a standard laboratory diet. One group received 200 pg/ml of Hg (as HgCl2) in deionised drinking water for 180 days and the other group was kept as a control. At the end of the exposure all the rats were placed in metabolism cages for the collection of 24 hour urine samples.The animals were anaesthetised with a single intraperitoneal injection of sodium thiopental (50 mg/kg body weight) in order to perform haemodynamic measurements. The trachea was cannulated to allow spontaneous breathing and polyethylene catheters (containing sodium heparin, 100 USP units/ml) were placed in the left femoral artery to record aortic blood pressure. Specimens of several tissues were also excised for histopathological observation by light microscopy.Samples of blood, brain, heart, and kidney were prepared for determination of Hg content. Mercury was analysed by flameless atomic spectrophotometry after special digestion of tissues and blood.25 The Hg content was quoted as the wet weight of blood and
The consistent alterations in diverse parameters of the kallikrein-kinin systems as recorded in hypertensive rats, suggest that kallikrein may be involved in the mechanism of hypertension. Not only urinary kallikrein (1, 2) but also kininogenase activity in the kidney are strikingly decreased either in Grollman or Goldblatt experimental models (3), while blood kininogen is increased (4).These findings do not provide definite evidence as to the role of the kallikrein-kinin system on the antihypertensive mechanism of the kidney but they reflect at least a reduced capacity of the kidney to produce or release kallikrein.The key role of the kidney on arterial hypertension is well known. It has been shown by performing renal transplants on rat strains with opposite genetic propensity for hypertension, that the kidney has genetic determinants on blood pressure (5, 12). Using the technique of selective inbreeding, starting from a single Wistar strain, Bianchi (6) obtained two separate lines: spontaneously hypertensive rats (SHR) and normotensive rats (NR), thus providing a unique possibility to study the changes occurring in genetic hypertension. Normotensive rats deriving from common ancestors were used as controls.We report here the levels of kallikrein activity found in these two lines of rats which are genetically related. Results show that urinary kallikrein is significantly decreased in hypertensive rats as compared to controls.Material and Methods. The technique used to obtain the hypertensive and normotensive strains was described elsewhere (6). A selective inbreeding was started in 1964 from an original Wistar strain (different from Oka-mot0 strain) to obtain a line of rats with high blood pressure. Later, and from the same strain, another line of rats with normal blood pressure was developed (6).In the present experiments, 38 2-mo-old rats were used (body wt 150-265 g) with blood pressures as follows: males, 10 hypertensive, 160-180 mmHg; 9 normal, 120-150 mmHg. Females, 10 hypertensive, 160-180 mmHg; 9 normal, 120-135 mmHg. Hypertensive rats were from the 25th generation and normotensive from the 24th generation.Blood pressure was measured at the tail by the method of Friebel and Vreden (7) after having preheated the animals in a warming box (8). Animals were fed with a normal salt diet (1 % NaCl). On the day of the experiment they were placed into individual metabolic cages, in order to collect the urine for 24 hr. An adequate device prevented urine contamination either with feces or food. 2 ml of toluene was introduced in each collecting recipient and at the end of the collection period the urine was measured and immediately frozen and kept at -20" until the kallikrein determinations.At weaning (21-25 days of age) the blood pressure of both NR and SHR strains does not differ. Later, the blood pressure of SHR increases more rapidly and a statistically significant difference (P < 0.01) between both strains appears at 35 days of age.Kallikrein determinations. Kallikrein activity was determined in each sample by...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.