Hypotension- and osmotically induced thirst in old Brown Norway rats

Abstract

Thunhorst RL, Beltz TG, Johnson AK. Hypotension-and osmotically induced thirst in old Brown Norway rats. Am J Physiol Regul Integr Comp Physiol 297: R149 -R157, 2009. First published May 6, 2009 doi:10.1152/ajpregu.00118.2009.-Compared to young cohorts, old rats drink less water in response to several thirst-inducing stimuli. In these experiments, we characterized water drinking in response to hypotension and cellular dehydration in young (4 mo), middle-aged adult (12 mo) and old (29 -30 mo) male Brown Norway rats. We injected the vasodilator, minoxidil as an intravenous bolus in a range of doses (0 -20 mg/kg), so that drinking responses could be compared at equivalent reductions of arterial pressure. Old rats had greatly diminished reflex tachycardia and became significantly more hypotensive after minoxidil compared with young and middle-aged rats. When compared at equivalent reductions of arterial pressure, old rats drank one-third as much as middle-aged rats, and one-fifth as much as young rats. In addition, there were age-related deficits in drinking in response to a range of administered loads of sodium (0.15-2 M NaCl, 2 ml/100 g body wt). Urinary excretion of water and sodium in response to the loads was equivalent across ages. Both middle-aged and old rats were less able than young rats to repair their water deficits after sodium loading, attributable almost entirely to their reduced drinking responses compared with young rats. Lastly, agerelated declines in drinking appeared to be more severe in response to hypotension than in response to cellular dehydration. aging; drinking; diuresis; natriuresis; dehydration; blood pressure; heart rate ELDERLY PEOPLE AND OLD ANIMALS have impaired drinking responses to many thirst-inducing challenges (21, 23, 25, 28, 29, 33-35, 40, 41). However, the nature of the underlying causes of reduced drinking that accompanies old age, such as impaired neural or humoral signaling mechanisms, remain largely undetermined. Knowledge of the causes of age-related declines in drinking will increase our understanding of the ways to help the elderly maintain better fluid homeostasis. This is an important consideration for an increasingly aging population and for the relationship between hydrational status and disorders, such as heat-related injury.Hypotension is a potent stimulus of thirst in rats (e.g., 10,17,18,26,30,38). Thirst following hypotension is due mainly to release of renin and formation of ANG II in the circulation (26, 38; for a review, see Ref. 20) and is blocked by interfering with the actions of, or formation of, ANG II (10,26,33,38). There are conflicting reports about whether old rats drink less in response to hypotension. For example, old rats have been found to drink less after subcutaneous injections of isoproterenol compared with young rats (24, 34, 37), although not always (25,34). These previous studies did not record arterial pressure or control for differences in arterial pressure that may occur with aging (24,25,34,37). This information is important becau...

Effects of aging on mineralocorticoid-induced salt appetite in rats

“…This finding differs considerably from observations of age-related declines in thirst for male BN rats. In response to several dipsogenic stimuli and taking BW into account, we find that young rats drink the most followed in descending order by middle-aged and old rats, although middle-aged rats sometimes drink no more than do old rats (44,45,47). Mineralocorticoids produce sodium ingestion by actions at central MRs either to directly stimulate salt appetite (14,35,36) or to reduce activity within a central system that inhibits salt appetite (41).…”

“…Changes in levels of these hormones with age are postulated to be a response to defective pressure-diuresis/natriuresis of the aging kidney, which may leave older animals slightly hypervolemic (50). In addition, baroreceptors are impaired in older animals beginning at least by middle age in the BN strain (e.g., 44,45,47). Thus there may be age-related differences in the generation of neural signals related to increased blood volume and blood pressure that could impact water and saline drinking in response to DOCA treatment.…”

“…As in the elderly, aging rats have reduced ability to concentrate urine (7,27) and drink less water in response to various experimental challenges to body fluid balance (5,25,31,32,38). For example, our laboratory has observed deficiencies in osmotic and renin-dependent thirsts in old rats (44,45,47,48,52). In addition, experimental studies find age-related deficits in salt appetite, the companion motivation to thirst, in response to sodium depletion in old rats of the Brown Norway (BN), Sprague-Dawley (SD), and Fischer 344 (F344) strains (5,32,48).…”

Effects of β-adrenergic receptor agonists on drinking and arterial blood pressure in young and old rats

“…Vasodilatory drugs (e.g., nitroprusside, minoxidil) typically cause greater hypotension in older, compared with younger, rats, which is attributable to impaired baroreflex function and diminished renin secretion in older animals (9,38). Despite comparable hypotension in all three groups, salbutamol clearly produced less tachycardia in old rats, and progressively reduced renin secretion in middle-aged and old rats compared with young rats.…”

“…However, the relative contributions of the ␤ 1 -and ␤ 2 -adrenergic receptor subtypes to age-related drinking have not been examined. Old rats have greatly impaired baroreflex mechanisms (2,9,18,32,38) and respond to ␤-adrenergic receptor activation with diminished tachycardia (1,6,35; but see Ref. 9) and attenuated renin secretion (4), which may affect drinking differently in old and young rats.…”