A colony of 26 chimpanzees given a fruit and vegetable diet of very low Na and high K intake were maintained in long-standing, socially stable small groups for three years. Half of them had salt added progressively to their diet during 20 months. This addition of salt within the human dietetic range caused a highly significant rise in systolic, mean and diastolic blood pressure. The change reversed completely by six months after cessation of salt. The effect of salt differed between chimpanzees, some having a large blood pressure rise and others small or no rise. These results in the species phylogenetically closest to humans bear directly on causation of human hypertension, particularly in relation to migration of preliterate people, with low Na diet, to a Western urban lifestyle with increased salt intake. The hedonic liking for salt and avid ingestion was apt during human prehistory involving hunter-gatherer-scavenger existence in the interior of continents with a scarcity of salt, but is maladaptive in urban technological life with salt cheap and freely available.

Polyunsaturated fatty acids (PUFA) are essential structural components of the central nervous system. Their role in controlling learning and memory has been well documented. A nutrigenomic approach with high-density microarrays was used to reveal brain gene-expression changes in response to different PUFA-enriched diets in rats. In aged rats fed throughout life with PUFA-enriched diets, genes with altered expressions included transthyretin, ␣-synuclein, and calmodulins, which play important roles in synaptic plasticity and learning. The effect of perinatal omega-3 PUFA supply on gene expression later in life also was studied. Several genes showed similar changes in expression in rats fed omega-3-deficient diets in the perinatal period, regardless of whether they or their mothers were fed omega-3 PUFA-sufficient diets after giving birth. In this experiment, among the down-regulated genes were a kainate glutamate receptor and a DEAD-box polypeptide. Among the up-regulated genes were a chemokine-like factor, a tumor necrosis factor receptor, and cytochrome c. The possible involvement of the genes with altered expression attributable to different diets in different brain regions in young and aged rats and the possible mode of regulatory action of PUFA also are discussed. We conclude that PUFA-enriched diets lead to significant changes in expression of several genes in the central nervous tissue, and these effects appear to be mainly independent of their effects on membrane composition. The direct effects of PUFA on transcriptional modulators, the downstream developmentally and tissue-specifically activated elements might be one of the clues to understanding the beneficial effects of the omega-3 PUFA on the nervous system.

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In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE ؊/؊ ) and compared with wild-type littermates. Compared with wild-type littermates, ACE ؊/؊ mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE ؊/؊ mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE ؊/؊ mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE ؊/؊ mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.fatty acid metabolism ͉ obesity ͉ ACE knockout mice ͉ glucose tolerance T he renin-angiotensin system (RAS) is important in both cardiovascular and body fluid homeostasis (1-3) and has recently been implicated in obesity and energy balance (see ref.4 for a review). All of the components of the RAS are present in adipose tissue and evidence suggests that this RAS is fully functional and can contribute to the accumulation of fat and to obesity (5-7). Recent studies showed that transgenic mice lacking the precursor peptide, angiotensinogen (AGT), have impaired weight gain and adipose tissue development (8), whereas mice with an overabundance of AGT in adipose tissue have markedly increased fat mass (9).Overexpression of genes associated with the RAS has been reported in human visceral adipose tissue in overweight subjects (10), and polymorphisms of the angiotensin-converting enzyme (ACE) gene have been linked to the incidence of obesity and alterations of body mass index (11,12). ACE plays a key role in the RAS in that it converts angiotensin I to the bioactive peptide angiotensin II (Ang II). Ang II has been identified as a trophic factor in the differentiation of preadipocytes to mature adipocytes (13). There is evidence that administration of ACE inhibitors reduces body weight gain in spontaneously hypertensive rats (14), obese Zucker rats (15), and humans (16). However, some studies have shown that the activity of the RAS is inversely related to the gain of body weight....

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The progression of animal life from the paleozoic ocean to rivers and diverse econiches on the planet's surface, as well as the subsequent reinvasion of the ocean, involved many different stresses on ionic pattern, osmotic pressure, and volume of the extracellular fluid bathing body cells. The relatively constant ionic pattern of vertebrates reflects a genetic "set" of many regulatory mechanismsparticularly renal regulation. Renal regulation of ionic pattern when loss of fluid from the body is disproportionate relative to the extracellular fluid composition (e.g., gastric juice with vomiting and pancreatic secretion with diarrhea) makes manifest that a mechanism to produce a biologically relatively inactive extracellular anion HCO3 exists, whereas no comparable mechanism to produce a biologically inactive cation has evolved. Life in the ocean, which has three times the sodium concentration of extracellular fluid, involves quite different osmoregulatory stress to that in freshwater. Terrestrial life involves risk of desiccation and, in large areas of the planet, salt deficiency. Mechanisms integrated in the hypothalamus (the evolutionary ancient midbrain) control water retention and facilitate excretion of sodium, and also control the secretion of renin by the kidney. Over and above the multifactorial processes of excretion, hypothalamic sensors reacting to sodium concentration, as well as circumventricular organs sensors reacting to osmotic pressure and angiotensin II, subserve genesis of sodium hunger and thirst. These behaviors spectacularly augment the adaptive capacities of animals. Instinct (genotypic memory) and learning (phenotypic memory) are melded to give specific behavior apt to the metabolic status of the animal. The sensations, compelling emotions, and intentions generated by these vegetative systems focus the issue of the phylogenetic emergence of consciousness and whether primal awareness initially came from the interoreceptors and vegetative systems rather than the distance receptors.In the higher mammals, the functions centered in the hypothalamus play a paramount role in integrating the many physiological systems controlling the milieu interieur. These hypothalamic processes range from genetically determined patterns of ingestive behavior that correct body deficits and, in turn, involve associated cognitive and memory functions of the cortex, to the other extreme of the control of excretory processes, in a mode apt to the metabolic status of the animal.Some evolutionary aspects of body fluid control will be described first as a general biological context of the mechanisms in mammals.Mountain building, like the Grand Canyon uplift in the Cambrian and subsidence in the Ordivician periods, provided conditions of rivers flowing into the ocean, and, probably during this time, protovertebrates with spindle body and segmentally arranged muscles adapted to rhythmic contractions evolved (reviewed in refs. 1 and 2). Later, irradiation of vertebrates from estuaries, rivers, and swamps involved pro...

Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 g͞h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxininduced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular subdivision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10 ؊7 M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10 ؊7 M angiotensin II. The data indicate that bloodborne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood-brain barrier may have regulatory influences on fluid balance during pregnancy in rats.R elaxin is a peptide hormone secreted by the corpus luteum of the ovary during pregnancy. Relaxin acts on reproductive tissues such as the pubic symphysis, uterus, and cervix (1, 2), but it may also influence the brain (3). Evidence of this influence is presented in reports that the intracerebroventricular (i.c.v.) (1) injection of relaxin results in stimulation of oxytocin and vasopressin secretion, water drinking, and a pressor response (3-8). i.c.v. administration of relaxin also stimulates increased expression of c-fos in groups of neurons in the supraoptic nucleus (SON) and hypothalamic paraventricular nucleus (PVN), as well as in the subfornical organ (SFO), median preoptic nucleus (MnPO), and organum vasculosum of the lamina terminalis (OVLT) (9). Circulating relaxin probably has endocrine actions on the brain, because high-affinity-binding sites for relaxin are present in the SFO and OVLT of the rat (10), two brain regions that are accessible to circulating relaxin because they lack a blood-brain barrier (11). Also, i.v. infusion of relaxin causes vasopressin secretion and water drinking in the rat, effects that may be mediated through brain angiotensinergic mechanisms (12,13). Evidence that relaxin [together with other hormones such as angiotensin II (Ang II) and vasopressin] plays a physiological role in regulating body fluid homeostasis d...

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