David R. Mouw

Lead: possible toxicity in urban vs rural rats

The degree of lead poisoning in wild rats from two environments has been studied. Wild rats captured in an urban area had markedly elevated tissue lead compared with values in rural rats. This elevation may have been caused by differences in factors affecting absorption of ingested lead or an elevated respiratory exposure to airborne lead, or both, and lead in precipitated dust. Changes in several biologic indexes (depression of delta-amino levulinic acid dehydratase in kidney and red blood cells, presence of renal intranuclear inclusion bodies, and increased kidney weight) confirmed lead-poisoning in urban rats.

Plasma Renin Activity in Psychosocial Hypertension of CBA Mice

We studied plasma renin activity (PRA) in male full-color brown Agouti (CBA) mice subjected to varying degrees of psychosocial stress induced by manipulation of their housing patterns. Blood samples were obtained from unanesthetized mice by retro-orbital puncture; blood pressure (BP) was measured by tail plethysmography. At 4 months of age, PRA was lower in mice isolated since weaning (isolates) than in mice housed together in standard cages (boxed sibs). Isolation of boxed sibs for 7 days also decreased PRA. PRA did not change in isolates during a 10-month period. In contrast, PRA and BP changed markedly after 4-month-old isolates were placed in an interconnected box system [population cage (PC)] which increased social interaction and competition; values at all times were greater than those of isolated controls. PRA increased rapidly during the first 1-2 days, declined from these high values over the next 3 weeks to values similar to those of boxed sibs (but higher than control isolates), and then rose again progressively during the next 5-6 months. BP was elevated within 1 week (particularly in subordinate mice), then rose slowly throughout the experiment. During the first 2 months, PRA and BP were inversely correlated; no significant correlation existed after 2 months. Hematocrit tended to be lower in PC mice from 7 days on. Blood urea was increased in 10-month-old PC mice. Increased PRA and BP also occurred in boxed sibs placed in PC for 3-10 weeks. The pattern of PRA changes in these mice is analogous to that observed in certain forms of human essential hypertension and is further evidence that psychosocial hypertension in CBA mice may be an appropriate model for the study of essential hypertension.

Psychosocial stimuli and human plasma renin activity.

&NA; The effects of several types of acute psychosocial stimuli on plasma renin activity (PRA) were studied in normotensive healthy subjects. Puzzle‐solving produced an increase in blood pressure but no significant change in PRA, although two of seven subjects did respond with large increases in PRA. Watching a disturbing movie also raised blood pressure, but did not alter PRA. In contrast, a combination of novelty, fear, and/or anticipation did constitute a significant stimulus for renin secretion; this was evidenced by the fact that naive subjects (who were not told in advance what to expect) had significantly higher PRAs on the first day of the 2‐day puzzle‐solving study. PRA on this day correlated strongly with anxiety proneness, as did the decrease from day 1 to day 2. We conclude that meaningful psychosocial stimuli can enhance renin secretion in susceptible individuals.

Acute effects of lead on renal electrolyte excretion and plasma renin activity

R., VANDER, A. J., Cox, J., AND FLEISCHER, N. (1978). Toxicol. Appl. Pharmacol. 46,435447. Since lead accumulates in the kidney and interferes with the renal transport of amino acids and glucose, we tested the hypothesis that acute doses of lead also reduce tubular electrolyte reabsorption and alter the secretion of renin. In sodium pentobarbital-anesthetized dogs, acute iv lead increased the excretion of sodium, potassium, calcium, and water, despite a constant glomerular filtration rate; therefore lead reduced the tubular reabsorption of these substances. Lead also caused an increase in plasma renin activity. The threshold dose of acutely administered lead necessary to elicit these responses was determined in dose-response experiments on unanesthetized rats; a dose of 0.1 mg of lead/kg was sufficient to cause significant increases in plasma renin and the renal excretion of sodium. Lead concentrations in the tissues of the rats were measured in samples taken immediately at the conclusion of the study; the threshold dose of lead was associated with very low blood lead ((5 pg/lOO ml) and kidney lead (1.2 fig/g wet wt). These effects of lead are discussed with regard to their possible clinical significance.

Dose-Response Relation of CSF Sodium and Renal Sodium Excretion, and Its Absence in Homozygous Brattleboro Rats

Constant intraventricular infusion (3.3--6.6 microliters/min) of artificial cerebrospinal fluid with sodium concentrations of 100, 150, 200, 250, 300, and 350 mM produced a linear dose-related change in renal sodium excretion in conscious, unrestrained Sprague-Dawley rats. The periventricular receptors stimulated were able to evoke substantial changes in body sodium balance; the 350 mM Na CSF produced an estimated 14% deficit in the content of Na in the extracellular fluid over a 5-hour infusion period. This is the first demonstration of such a dose-response relation over a wide range of CSF Na concentration (above and below normal) in conscious animals. Both the dose-response relation, and the magnitude of the effects, suggests an important physiologic role for this control mechanism. The natriuresis in response to 300 mM sodium infusion was identical in Long-Evans Brattleboro rats heterozygous for diabetes insipidus (DI), and in Sprague-Dawley rats, but was completely absent in homozygous animals. Although the experimental methods (conscious unrestrained rats) precluded simultaneous evaluation of efferent pathways other than antidiuretic hormone (ADH), the evidence from the DI rats suggests that ADH may be the efferent pathway for the response.

Nonpressor mechanisms in CNS-induced natriuresis.

Ventriculocisternal perfusion was performed in pentobarbital-anesthetized dogs. Perfusion of high Na (300 mM NaCl) artificial cerebrospinal fluid (CSF) (E) for 2 h was preceded by 2 h of control (C) and was followed by 2 h of recovery (R) during which normal (150 mM NaCl) artificial CSF was perfused. A time-control group was perfused with normal artificial CSF throughout C, E, and R. High sodium perfusion resulted in a marked natriuresis in each of nine animals and suppression of plasma renin activity. Theere were no simultaneous changes in mean arterial pressure, glomerular filtration rate, or renal plasma flow. Sodium excretion and plasma renin activity showed a slight gradual rise in the time-control group, but no significant differences were observed between the C and E periods; sodium excretion and plasma renin activity were similar in the high Na and time-control groups during C and R, but significantly different during E. It is concluded that when CSF sodium is elevated by perfusing artificial CSF, the resulting natriuresis and suppression of plasma renin activity are not caused by hemodynamic changes.

Effect of parathyroid hormone on renin secretion.

Abstract The ability of parathyroid hormone (PTH) to increase renin secretion was investigated in pentobarbital-anesthetized dogs. An intravenous infusion of bovine PTH 1-34, at the dose of 0.028 μg kg-1 min-1 increased renin secretion by 149% (501 ± 105 to 1249 ± 309 ng hr-1 min-1); renin secretion returned to control values during the recovery period. In order to determine whether PTH acted directly on the kidney to increase renin secretion, PTH was infused into the right renal artery at doses of 0.0014 to 0.0028 μg kg-1 min-1 and renin secretion from the right kidney was compared to that from the left (control) kidney. Renin secretion from the right (PTH-infused) kidney was not greater than control values for that kidney or different from the renin secretory rate of the left (control) kidney. In contrast, the excretion rates of both phosphate and sodium from the right kidney were greater than control values and from the excretion rates of the left kidney. These data suggest that PTH, while acting directly on the kidney to increase phosphate and sodium excretion, does not elevate renin secretion by a direct renal action.

The effect of parathyroid hormone on the renal accumulation of lead

Abstract The effect of parathyroid hormone (PTH) on renal accumulation of lead has been assessed in two experiments on mature rats. In the first experiment, lead was given per os, followed by subcutaneous injections of PTH (100 units of parathyroid extract, Lilly) or vehicle alone over the next 2 days. In the second experiment, anesthetized rats were given lead ± PTH (bovine 1–34, Beckman; primed with 1.33 μg and a constant infusion of 4.2 ng/minute) intravenously over a 2-hour period. In both experiments, PTH caused significant increments in renal lead concentration (52 and 29%, respectively) compared to groups treated with lead but not PTH. Since total body lead is also increased with PTH treatment in the first experiment, a gastrointestinal (GI) mechanism is suggested; however, stimulation of GI absorption cannot account for the effect in the second experiment in which lead was administered iv. In both experiments, the increment in renal lead in the absence of changes in lead in other soft tissues (liver, red cell, or plasma) suggests a selective effect of PTH on renal lead. The possible mechanisms for this effect are discussed.

HYPOTHALAMIC STIMULATION OF ADH RELEASE BY ANGIOTENSIN II

Publisher Summary This chapter explores the role of renin–angiotensin system in the maintenance of both blood pressure and the salt and water balance of the body. Angiotensin is the most potent vasopressor substance known and the stimulation of aldosterone secretion it one of its major actions. Renin–angiotensin system plays a very wide-ranging role in the maintenance of body salt and water metabolism. Angiotensin is one of the normal controllers of antidiuretic hormone secretion. To test the hypothesis that the two were in some way linked, a simple series of experiments was designed on anesthetized dogs in which cannulae were placed in the cerebral ventricles in such a manner that it perfused artificial cerebral spinal fluid through the ventricular cisternal system.

The effect of chronic, low-level lead poisoning on the erythropoietin response to hypoxia.

Anemia is a characteristic of chronic lead-poisoning (1). Although lead might cause anemia solely via its known interference with hemoglobin synthesis (1), lead might also affect the kidneys secretion of erythropoietin (ESF) since lead accumulates in the kidney (2) and is known to impair other renal functions (3). Moreover, with regard to the kidneys endocrine function, we have recently demonstrated that small, acute, iv doses of lead (0.1 mg/kg) raise plasma renin activity (PRA); in contrast, chronic lead poisoning in humans on low salt diets is associated with relatively low PRA (4, 5). There have been no studies of ESF in chronic lead poisoning, but in rats, extremely large, acute, iv doses of lead (40 mg/kg) either reduce (6) or have no effect on (7) the plasma ESF response to hypoxia on the subsequent day. We therefore hypothesized that chronic, low-level, lead-poisoning would reduce the ESF response normally seen in hypoxia; we have tested this hypothesis in rats. Methods. Experimental protocol. Studies were performed on 48 male Sprague-Dawley rats weighing 355-469 g at the start of the study. For a 6-week period, four groups of 12 rats ate regular rat chow (Tecklad) and drank distilled water containing no lead (Group C-control or non-lead), 0.2 mg Pb/ml as lead acetate (group L,-low dose), 0.4 mg Pb/ml (group M-Medium dose), or 0.6 mg Pb/ml (group H-High dose). Rats were housed four to a cage, and daily fluid intake in each group-cage was measured throughout the six weeks. Thereafter, rats were transferred at 1400 hr to one of two pressure chambers, each of which could accommodate eight rats; food and water were available, Two rats from each of the 4 groups were placed in each chamber; for the next 22 hr pressure was left at atmospheric in one