Zinc and copper in tissues of rats with blood hypertension induced by long-term lead exposure.

Male Sprague-Dawley rats received for 14 months 0, 15, 30 and 60 micrograms/ml of lead in drinking water. Both blood pressure and tissue lead were augmented with a dose-response effect, while cardiac inotropism was increased only in the rats treated with 60 ppm of lead. In the exposed animals, zinc and copper were unchanged in kidneys and testicles and augmented in the brain, while copper, but not zinc, was reduced in the heart. These data suggest a possible relation between the modifications of copper and zinc metabolism and the effects of lead on cardiovascular homeostasis.

Copper deficiency effects on cardiovascular system and lipid metabolism in the rat; the role of dietary proteins and excessive zinc.

Weanling rats were fed a copper-deficient purified diet. The effects of varying the type of protein and supplements of copper and zinc on cardiovascular pathology and some biochemical parameters were investigated. It was found that cardiomyopathy developed in the copper-deficient groups. Milk powder caused significant exacerbation of this development relative to dietary casein or egg white. Angiopathy developed only when dietary zinc was 20 ppm. Dietary copper did not change this situation. Serum cholesterol was elevated when copper was low and casein or milk powder were the protein source. The data point to an interaction between type of protein and dietary copper or zinc in the pathogenesis of cardiovascular lesions.

Mechanisms in cardiovascular regulation following chronic exposure of male rats to inorganic mercury.

In this study we verified the possibility that chronic exposure to inorganic mercury may induce hemodynamic changes in the rat by affecting some neurogenic and/or humoral mechanisms regulating cardiovascular function. For this reason, aortic blood pressure, maximum rate of rise of the left ventricular pressure, heart rate, and electrocardiogram were monitored under pentothal anesthesia in rats which received 50 micrograms/ml of mercury (as HgCL2) in drinking water for 320 days and in control rats. No pressor or electrocardiographic changes were found in mercury-treated animals, which showed increase of cardiac inotropism and decrease of the pressor and inotropic responses to bilateral carotid occlusion. Cardiovascular responses to bilateral vagotomy and iv hexamethonium under vagotomy were unchanged in the mercury-exposed rats. In these animals both pressor and inotropic responses to iv norepinephrine and to higher doses of epinephrine were reduced, while the vascular beta-adrenergic response to 0.125 micrograms/kg of iv epinephrine was potentiated. Cardiovascular responses to acetylcholine, angiotensin I, angiotensin II, bradykinin, histamine, and serotonin did not differ in the two groups of rats. These results indicated that chronic mercury exposure affects cardiovascular function by interfering with the baroreflex mechanisms and/or the reactivity to catecholamines. Higher amounts of mercury were found in kidney, but the metal was significantly accumulated also in urine, blood, and brain. Mercury exposure greatly increased the levels of copper and zinc, but not that of iron, in brain and kidney. The increased accumulation of copper and zinc in tissues may be related in part to the mercury-induced synthesis of metallothionein, a protein able to bind these essential metals. It may be suggested that zinc and copper interact with mercury in inducing cardiovascular changes.

Urinary kallikrein and hypertension in cadmium-exposed rats.

Chronic exposure of rats to cadmium (Cd) in drinking water induced elevated systolic and diastolic blood pressure. Heart rate, however, was lowered, suggesting that the hypertension in these rates may be due to an increase of the total peripheral resistance, possibly involving a central nervous system (CNS) component in Cd-induced hypertension. Urinary kallikrein activity was reduced in the exposed animals and may explain the previously reported antinatriuretic effect of Cd, since renal kallikrein is an enzyme responsible for the synthesis of kallidin, a potent vasodilator and natriuretic polypeptide.

Lead, zinc, and erythrocyte delta-aminolevulinic acid dehydratase: relationships in lead toxicity.

A lead-intoxicated patient with extremely high blood lead levels and unexpectedly mild symptoms was studied prior to and following treatment with calcium disodium edetate (ethylenediaminetetraacetic acid) and then prior to and following oral administration of zinc sulfate. During chelation therapy, erythrocyte (delta)-aminolevulinic acid dehydratase (ALAD) activity decreased as blood lead levels fell. Urinary excretion of zinc increased and was more than 3.5 times greater than that of lead. The ratio of blood lead to serum zinc was greatest (1.47) when ALAD activity was lowest. Oral administration of zinc sulfate following chelation therapy resulted in a significant increase in mean ALAD activity. In vitro additions of zinc chloride to the patient's erythrocytes resulted in reactivation of ALAD activity. These studies suggest that zinc is an important element in the ALAD system in man. Zinc may play a protective role in lead toxicity, and zinc supplementation may be a useful adjunct to chelation therapy for lead toxicity.

Tyrosinemia with acute intermittent porphyria: aminolevulinic acid dehydratase deficiency related to elevated urinary aminolevulinic acid levels.

A patient who had hereditary tyrosinemia was observed during two illnesses to have characteristics of acute intermittent porphyria with associated hypertension. Metabolic studies revealed elevated levels of urinary aminolevulinic acid but normal levels of porphyrin metabolites associated with, and possibly explained by, decreased red blood cell activity of the zinc-dependent enzyme, aminolevulinic acid dehydratase. Zinc deficiency could not be directly associated with the diminished enzyme activity. The patient's hypertension appeared to be related to increased urinary excretion of catecholamines and to elevated renin activity in peripheral venous blood.

Biologic effects of auto emissions. I. Exhaust from engine with and without catalytic converter.

This paper relates to the efficacy of a catalytic converter in reducing the levels of certain pollutants emitted from an automobile engine and to the reduction and/or elimination of gross biologic damages in animals exposed to emissions from an exhaust system containing such catalysts. Groups of rats were exposed to diluted emissions from an automobile engine with and without catalyst. Concomitantly, a comparative experiment was conducted by exposing a group of rats to carbon monoxide alone (575 mg/m3). The parameters measured included hematocrit, serum LDH, GOT, and lysozyme. An elevation in hematocrit was observed in animals of the experiment run without catalyst and in those exposed to carbon monoxide; the use of the catalyst reduced the carbon monoxide levels in the exposure chambers by more than tenfold and prevented these bioeffects from occurring. Serum LDH activity was elevated in the groups of rats in the experiment conducted without catalyst, but no alternation was observed in the animals from the experiment utilizing the catalyst or in those exposed to carbon monoxide alone. The data obtained in this study showed that acute exposure to noncatalytic emissions caused significant alterations in certain biologic parameters. Conversely, the introduction of an oxidizing catalytic converter into the engine exhaust system reduced or prevented such biologic damage.