Search

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, age-related 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

Glucocorticoids [e.g., corticosterone and dexamethasone (Dex)], when administered systemically, greatly increase water drinking elicited by angiotensin and sodium ingestion in response to mineralocorticoids [e.g., aldosterone and deoxycorticosterone acetate (DOCA)], possibly by acting in the brain. In addition, glucocorticoids exert powerful renal actions that could influence water and sodium ingestion by promoting their excretion. To test this, we determined water and sodium intakes, excretions, and balances during injections of Dex and DOCA and their coadministration (DOCA+Dex) at doses commonly employed to stimulate ingestion of water and sodium. In animals having only water to drink, Dex treatment greatly increased water and sodium excretion without affecting water intake, thereby producing negative water and sodium balances. Similar results were observed when Dex was administered together with DOCA. In animals having water and saline solution (0.3 M NaCl) to drink, Dex treatment increased water and sodium excretion, had minimal effects on water and sodium intakes, and was associated with negative water and sodium balances. DOCA treatment progressively increased sodium ingestion, and both water and sodium intakes exceeded their urinary excretion, resulting in positive water and sodium balances. The combination of DOCA +Dex stimulated rapid, large increases in sodium ingestion and positive sodium balances. However, water excretion outpaced total fluid intake, resulting in large, negative water balances. Plasma volume increased during DOCA treatment and did not change during treatment with Dex or DOCA+Dex. We conclude that increased urinary excretion, especially of water, during glucocorticoid treatment may explain the increased ingestion of water and sodium that occurs during coadministration with mineralocorticoids. thirst; urine volume; dexamethasone; deoxycorticosterone acetate; food intake

Depression is an important public health problem and is considered to be an independent risk factor for coronary artery disease. The pathophysiological mechanisms that link depression with adverse cardiovascular events (e.g., myocardial ischemia, myocardial infarction, and sudden death) are not well established. It is possible that an increased susceptibility to life-threatening cardiac arrhythmias in depressed patients influences the risk of morbidity and mortality in coronary artery disease. This idea was tested with the use of an experimental model of depression that was developed to induce anhedonia, the reduced responsiveness to pleasurable stimuli observed in human depressed patients. Rats exposed to 4 wk of chronic mild stress (e.g., paired housing, strobe light, and white noise) displayed anhedonia, which was operationally defined by the reduced intake of a palatable sucrose solution relative to an established baseline and to control animals. Furthermore, compared with control rats, the anhedonic rats showed increased basal heart rate and decreased heart rate variability. In response to an intravenously infused chemical challenge, aconitine, anhedonic rats exhibited an increased vulnerability to ventricular arrhythmias, as indicated by a reduced threshold for premature ventricular complexes, salvos, and ventricular tachycardia. These findings suggest that the presence of depressive symptoms is associated with a lower threshold for ventricular arrhythmias, which may contribute to the increased risk for adverse cardiovascular events in patients with depression. aconitine: animal models; chronic mild stress; coronary artery disease; electrocardiogram; heart rate variability; rats

To examine the behavioral and neural control of body fluid homeostasis, water and saline intake of C57BL/6 mice was monitored under ad libitum conditions, after treatments that induce water or salt intake, and after ablation of the periventricular tissue of the anteroventral third ventricle (AV3V). Mice have nocturnal drinking that is most prevalent after the offset and before the onset of lights. When given ad libitum choice, C57BL/6 mice show no preference for saline over water at concentrations up to 0.9% NaCl and a progressive aversion to saline above that concentration. Systemic hypertonic saline, isoproterenol, and polyethylene glycol treatments are dipsogenic; however, systemic ANG II is not. Intracerebroventricular injections of both hypertonic saline and ANG II are dipsogenic, and diuretic treatment followed by a short period of sodium deprivation induces salt intake. After ablation of the AV3V, mice can be nursed to recovery from initial adipsia and, similar to rats, show chronic deficits to dipsogenic treatments. Taken together, the data indicate that mechanisms controlling thirst in response to cellular dehydration in C57BL/6 mice are similar to rats, but there are differences in the efficacy of extracellular dehydration-related mechanisms, especially for systemic ANG II, controlling thirst and salt appetite. AV3V ablation; drinking; homeostasis; rhythms; sodium appetite; thirst

Water deprivation-induced sodium appetite: humoral and cardiovascular mediators and immediate early genes. Am J Physiol Regulatory Integrative Comp Physiol 282: R552-R559, 2002; 10.1152/ ajpregu.00295.2000. Adult rats deprived of water for 24-30 h were allowed to rehydrate by ingesting only water for 1-2 h. Rats were then given access to both water and 1.8% NaCl. This procedure induced a sodium appetite defined by the operational criteria of a significant increase in 1.8% NaCl intake (3.8 [+ or -] 0.8 ml/2 h; n = 6). Expression of Fos (as assessed by immunohistochemistry) was increased in the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO), subfornical organ (SFO), and supraoptic nucleus (SON) after water deprivation. After rehydration with water but before consumption of 1.8% NaCl, Fos expression in the SON disappeared and was partially reduced in the OVLT and MnPO. However, Fos expression did not change in the SFO. Water deprivation also 1) increased plasma renin activity (PRA), osmolality, and plasma [Na.sup.+]; 2) decreased blood volume; and 3) reduced total body [Na.sup.+]; but 4) did not alter arterial blood pressure. Rehydration with water alone caused only plasma osmolality and plasma [Na.sup.+] concentration to revert to euhydrated levels. The changes in Fos expression and PRA are consistent with a proposed role for ANG II in the control of the sodium appetite produced by water deprivation followed by rehydration with only water. salt intake; hypovolemia; circumventricular organs; dehydration; thirst

The hypothesis that the tissue surrounding the anteroventral part of the third ventricle (AV3V) plays a role in the expression of the pressor responses produced by systematically injected excitatory amino acid (EAA) analogs was studied. Specifically, prior electrolytic ablation of the AV3V region was examined if it would affect the pressor responses to kainic acid and N-methyl-D-aspartate. The results showed that EAA analogs produced pressor responses by stimulation of EAA receptors which suggest that the AV3V region may play an important role in these responses.

Need-free appetite for sodium in rats was studied by analyzing lesions of dorsomedial medulla. Area postremia (AP)-centered lesions increased concentrated saline solution intake, electrolyte and water excretion. Dipsogenic challenges evoked similar behavioral reaction as extracellular fluid depletion. Enhanced saline solution consumption was unrelated to thedepletion of sodium. Excessive sodium and water intake, causing rise in extracellular fluid volume, is regulated by the AP and dorsomedial medulla.

Agonist activation of cytosolic [Ca.sup.2+] in subfornical organ cells projecting to the supraoptic nucleus. Am J Physiol Regulatory Integrative Comp Physiol 280: R1592-R1599, 2001.--The subfornical organ (SFO) is sensitive to both ANG II and ACh, and local application of these agents produces dipsogenic responses and vasopressin release. The present study examined the effects of cholinergic drugs, ANG II, and increased extracellular osmolarity on dissociated, cultured cells of the SFO that were retrogradely labeled from the supraoptic nucleus. The effects were measured as changes in cytosolic calcium in fura 2-loaded cells by using a calcium imaging system. Both ACh and carbachol increased intracellular ionic calcium concentration ([[Ca.sup.2+].sub.i]). However, in contrast to the effects of muscarinic receptor agonists on SFO neurons, manipulation of the extracellular osmolality produced no effects, and application of ANG II produced only moderate effects on [[Ca.sup.2+].sub.i] in a few retrogradely labeled cells. The cholinergic effects on [[Ca.sup.2+].sub.i] could be blocked with the muscarinic receptor antagonist atropine and with the more selective muscarinic receptor antagonists pirenzepine and 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP). In addition, the calcium in the extracellular fluid was required for the cholinergic-induced increase in [[Ca.sup.2+].sub.i]. These findings indicate that ACh acts to induce a functional cellular response in SFO neurons through action on a muscarinic receptor, probably of the [M.sub.1] subtype and that the increase of [[Ca.sup.2+].sub.i], at least initially, requires the entry of extracellular [Ca.sup.2+]. Also, consistent with a functional role of [M.sub.1] receptors in the SFO are the results of immunohistochemical preparations demonstrating [M.sub.1] muscarinic receptor-like protein present within this forebrain circumventricular organ. cholinergic; muscarinic angiotensin II; osmosensitive magnocellular neurons; vasopressin; oxytocin

Numerous findings demonstrate that there is a strong association between maternal health during pregnancy and cardiovascular disease in adult offspring. The purpose of the present study was to test whether maternal gestational hypertension modulates brain renin-angiotensin-aldosterone system (RAAS) and proinflammatory cytokines that sensitizes angiotensin II-elicited hypertensive response in adult offspring. In addition, the role of renal nerves and the RAAS in the sensitization process was investigated. Reverse transcription polymerase chain reaction analyses of structures of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAAS components and proinflammatory cytokines in 10-week-old male offspring of hypertensive dams. Most of these increases were significantly inhibited by either renal denervation performed at 8 weeks of age or treatment with an angiotensin-converting enzyme inhibitor, captopril, in drinking water starting at weaning. When tested beginning at 10 weeks of age, a pressor dose of angiotensin II resulted in enhanced upregulation of mRNA expression of RAAS components and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented pressor response in male offspring of hypertensive dams. The augmented blood pressure change and most of the increases in gene expression in the offspring were abolished by either renal denervation or captopril. The results suggest that maternal hypertension during pregnancy enhances pressor responses to angiotensin II through overactivity of renal nerves and the RAAS in male offspring and that upregulation of the brain RAAS and proinflammatory cytokines in these offspring may contribute to maternal gestational hypertension-induced sensitization of the hypertensive response to angiotensin II. [ABSTRACT FROM AUTHOR]