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Age-associated alterations in thirst and arginine vasopressin in response to a water or sodium load

Age and Ageing, March, 1995 by Ioan Davies, Paul A. O'Neill, Kathleen A. McLean, James Catania, Derek Bennett

Introduction

There are marked age-associated changes in the regulation of water metabolism. Some authors hold the view that in humans ageing is accompanied by a mild form of diabetes insipidus [1]. Early experimental studies in laboratory rodents tended to support this idea [2], and the diabetes insipidus was linked to a reduction in the release of arginine vasopressin (AVP) from the posterior pituitary. In addition, there was a decrease in plasma AVP levels in old rats. Conversely, recent studies have not shown a decrease in neurohypophysial function with increasing age [2].

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The evidence for an age-associated difference in the basal plasma AVP of healthy humans is contradictory. Some studies show no change in plasma AVP between young and old men [3-5], although others have found an increase [6]. Old age is also thought to be accompanied by increased osmoreceptor sensitivity [3]. Thus, in one study of elderly people there was a greater release of AVP in response to increasing plasma osmolality [3], although the age range of the subjects was only 52-66 years. Others [7] found a diminished AVP response to water deprivation in a much older population (mean age 76 years). A more recent investigation of the response of plasma AVP to hypertonic saline infusion failed to detect a difference between young and old groups [8]. In the light of these contradictory findings further work is necessary to understand age-associated changes in the physiological variables involved in water homoeostasis.

A major element in the preservation of water balance is thirst, and this was not measured in earlier studies [3, 7]. It is a common belief that thirst decreases with age [9] and this has been reported after water deprivation of healthy, elderly men [10]. These findings were confirmed when old men were studied in the periods immediately following water [11], or osmotic loads [8]. However, to our knowledge, water homoeostasis has only been examined in small numbers of elderly men [8, 10, 11], whose precise health status was not defined [12].

Research in our laboratory has confirmed that elderly people are vulnerable to disturbances of hydration. A high plasma osmolality was associated with a marked increase in mortality in long-term-care patients [13]. Others have shown elderly people predisposed to both hypo- and hypernatraemic states with consequent morbidity and mortality [14]. However, because of the contradictions in the published data on water conservation in older people it is impossible to determine whether the changes observed are due to the ageing, or to the age-associated pathology of these subjects. There is a need to clarify whether there are changes in water homoeostasis with age because it is known that age-associated pathology and chronic disability can influence the measurement of age changes [12]. In this study we defined the health status of our elderly subjects using an established protocol, and examined simultaneous changes in thirst, plasma osmolality and AVP during sodium and water loading.

Methods

Subjects

Ten elderly subjects ([greater than] 70 years) were recruited from a panel of people who had previously been examined to define their health status according to set criteria (see Appendix I [12]). We screened a total of 20 elderly people randomly chosen from this panel. Their plasma and urine osmolality were measured on two consecutive days and their creatinine clearance estimated from a 24-hour urine sample. Four subjects were excluded because their clearance was [less than] 60 ml/min. Ten subjects were randomly chosen from the remainder.

The elderly subjects were compared with ten younger volunteers ([less than] 40 years), who had no history of chronic disease, were free of medication at the time of study and unaware of the aims of the research. The protocol for the study was approved by the Ethical Committee of Salford District Health Authority.

Manipulation of A VP Secretion and Thirst

Pre-experimental conditions: The stimuli used to examine the thirst and AVP response to alterations in plasma osmolality (pOsm) were an oral water load and a hypertonic saline infusion. The order of administration was decided randomly, and at least one week elapsed between studies on each subject. Subjects did not smoke, drink alcohol or take caffeine from 21 h 00 on the night before the study, when 250ml of water was drunk. A light breakfast, with a further 250ml of water, was consumed on the morning of the study. No other fluids were allowed in the 12 hours before each experiment. This method was an attempt to standardize the water status of the subjects as far as possible.

Water loading: Subjects attended the laboratory at 08 h 30, a baseline urine sample was obtained and the volume and osmolality recorded. The subjects were placed in a recumbent position and a venous cannula (21 G, Venflon) inserted into the antecubital fossa. After a further 30 min recumbency two basal blood samples (15 min apart) were taken for haematocrit, plasma sodium, creatinine, urea, osmotic pressure and AVP. Thirst was also assessed (see below).

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Age-associated alterations in thirst and arginine vasopressin in response to a water or sodium load

Age and Ageing, March, 1995 by Ioan Davies, Paul A. O'Neill, Kathleen A. McLean, James Catania, Derek Bennett

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