Early detection of metabolic and energy disorders by thermal time series stochastic complexity analysis

Maintenance of thermal homeostasis in rats fed a high-fat diet (HFD) is associated with changes in their thermal balance. The thermodynamic relationship between heat dissipation and energy storage is altered by the ingestion of high-energy diet content. Observation of thermal registers of core temperature behavior, in humans and rodents, permits identification of some characteristics of time series, such as autoreference and stationarity that fit adequately to a stochastic analysis. To identify this change, we used, for the first time, a stochastic autoregressive model, the concepts of which match those associated with physiological systems involved and applied in male HFD rats compared with their appropriate standard food intake age-matched male controls (n=7 per group). By analyzing a recorded temperature time series, we were able to identify when thermal homeostasis would be affected by a new diet. The autoregressive time series model (AR model) was used to predict the occurrence of thermal homeostasis, and this model proved to be very effective in distinguishing such a physiological disorder. Thus, we infer from the results of our study that maximum entropy distribution as a means for stochastic characterization of temperature time series registers may be established as an important and early tool to aid in the diagnosis and prevention of metabolic diseases due to their ability to detect small variations in thermal profile.

Maternal undernutrition and the offspring kidney: from fetal to adult life

Maternal dietary protein restriction during pregnancy is associated with low fetal birth weight and leads to renal morphological and physiological changes. Different mechanisms can contribute to this phenotype: exposure to fetal glucocorticoid, alterations in the components of the renin-angiotensin system, apoptosis, and DNA methylation. A low-protein diet during gestation decreases the activity of placental 11ß-hydroxysteroid dehydrogenase, exposing the fetus to glucocorticoids and resetting the hypothalamic-pituitary-adrenal axis in the offspring. The abnormal function/expression of type 1 (AT1R) or type 2 (AT2R) AngII receptors during any period of life may be the consequence or cause of renal adaptation. AT1R is up-regulated, compared with control, on the first day after birth of offspring born to low-protein diet mothers, but this protein appears to be down-regulated by 12 days of age and thereafter. In these offspring, AT2R expression differs from control at 1 day of age, but is also down-regulated thereafter, with low nephron numbers at all ages: from the fetal period, at the end of nephron formation, and during adulthood. However, during adulthood, the glomerular filtration rate is not altered, due to glomerulus and podocyte hypertrophy. Kidney tubule transporters are regulated by physiological mechanisms; Na+/K+-ATPase is inhibited by AngII and, in this model, the down-regulated AngII receptors fail to inhibit Na+/K+-ATPase, leading to increased Na+ reabsorption, contributing to the hypertensive status. We also considered the modulation of pro-apoptotic and anti-apoptotic factors during nephrogenesis, since organogenesis depends upon a tight balance between proliferation, differentiation and cell death.

Consequences of cerebroventricular insulin injection on renal sodium handling in rats: effect of inhibition of central nitric oxide synthase

In the present study, we investigated the effects of acute intracerebroventricular (icv) insulin administration on central mechanisms regulating urinary sodium excretion in simultaneously centrally NG-nitro-L-arginine methylester (L-NAME)-injected unanesthetized rats. Male Wistar-Hannover rats were randomly assigned to one of five groups: a) icv 0.15 M NaCl-injected rats (control, N = 10), b) icv dose-response (1.26, 12.6 and 126 ng/3 µL) insulin-injected rats (N = 10), c) rats icv injected with 60 µg L-NAME in combination with NaCl (N = 10) or d) with insulin (N = 10), and e) subcutaneously insulin-injected rats (N = 5). Centrally administered insulin produced an increase in urinary output of sodium (NaCl: 855.6 ± 85.1 Ä percent/min; 126 ng insulin: 2055 ± 310.6 Ä percent/min; P = 0.005) and potassium (NaCl: 460.4 ± 100 Ä percent/min; 126 ng insulin: 669.2 ± 60.8 Ä percent/min; P = 0.025). The urinary sodium excretion response to icv 126 ng insulin microinjection was significantly attenuated by combined administration of L-NAME (126 ng insulin: 1935 ± 258.3 Ä percent/min; L-NAME + 126 ng insulin: 582.3 ± 69.6 Ä percent/min; P = 0.01). Insulin-induced natriuresis occurred by increasing post-proximal sodium excretion, despite an unchanged glomerular filtration rate. Although the rationale for decreased urinary sodium excretion induced by combined icv L-NAME and insulin administration is unknown, it is tempting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 ± 67 æL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 ± 26 æL min-1 100 g body weight-1) and captopril-treated (903 ± 72 æL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019 percent compared to 0.126 ± 0.041 and 0.66 ± 0.015 percent in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05 percent) was significantly lower (P = 0.0063) than in control (0.91 ± 0.15 percent) and captopril-treated rats (1.24 ± 0.30 percent), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats

Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 æl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g). The icv cannula site was visually confirmed by 2 percent Evans blue infusion. Centrally administered insulin (42.0 ng/æl) increased the urinary output of sodium (from 855.6 ± 85.1 to 2055 ± 310.6 delta percent/min; N = 11) and potassium (from 460.4 ± 100 to 669 ± 60.8 delta percent/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 æg/3 æl) administration (from 628 ± 45.8 to 617 ± 87.6 delta percent/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 æg/3 æl) (from 498 ± 39.4 to 517 ± 73.2 delta percent/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways

A high-fructose diet induces insulin resistance but not blood pressure changes in normotensive rats

Rats fed a high-fructose diet represent an animal model for insulin resistance and hypertension. We recently showed that a high-fructose diet containing vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver and muscle of normal rats. In the present study, we examined the mean blood pressure, serum lipid levels and insulin sensitivity by estimating in vivo insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml of 6 æg insulin, iv) followed by calculation of the rate constant for plasma glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high-fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1 sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K for the control and high-fructose diets had no effect on insulin sensitivity measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats receiving the control and high-fructose diets from 117 + or - 3 and 118 + or - 3 mmHg to 141 + or - 4 and 132 + or - 4 mmHg (P<0.05), respectively. Triacylglycerol levels were higher in both groups treated with a high-fructose diet when compared to controls (C 1:3 R Na:K: 1.2 + or - 0.1 mmol/l vs F 1:3 R Na:K: 2.3 + or - 0.4 mmol/l and CNa 1:1 R Na:K: 1.2 + or - 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 + or - 0.4 mmol/l, P<0.05). These data suggest that fructose alone does not induce hyperinsulinemia or hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in the diet may contribute to the elevated blood pressure in this animal model

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 + or - 6.0 to 149 + or - 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 + or - 18 to 222 + or - 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 + or - 0.04 to 1.62 + or - 0.35 per cent (P<0.05) and in sodium post-proximal fractional excretion from 0.54 + or - 0.09 to 4.7 + or - 0.86 per cent (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 + or - 0.04 to 4.5 + or - 1.6 per cent and from 0.1 + or - 0.015 to 1.21 + or - 0.37 per cent, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

Myocardial contractile response to an oral glucose load in normal subjects evaluated by echocardiography

There is a paucity of experimental data on the actual mechanism of insulin-induced changes on the myocardial function. In the present study we investigated the myocardial contractile, response to an oral glucose load using echocardiography. Fifteen healthy volunteers were studied after overnight fast and 150 minutes after the oral load of 75 g glucose. Oral glucose load caused an increase in plasma glucose and insulin levels, which was accompained by a significant increase in left ventricular shortening (from 35.2 + 0.7 per cent at baseline, to 38.5 + 0.6 per cent and 39 + 0.9 per cent at 30 and 60 minutes post glucose load, respectively [P<0.05 vs baseline]; ejection faction rose from 0.73 per cent + 0.01 to 0.77 per cent + 0.01 (P<0.05); pressure rate product increased from 7.29 + 0.2 to 8.31 + 0.3 mmHg x beats per min (P<0.007) and heart rate enhanced from 68.3 + 1.9 to 74 + 1.6 (P<0.034) and 75.3 + 1.5 beats per min (P<0.008) at 60 and 90 minutes after glucose, respectively. Meanwhile, mean arterial presure decreased significantly (10+1.5 per cent, P<0.018) when compared to basal values. These results indicate a significant change in the myocardial contractile response to an oral glucose load, probably related to baroreceptor reflex response as well as an overridden by a potent vasodilatador action of insulin. Nevertheless, we could not rule out the cardiac effects may also be due an insulin-induced sympathetic activation or a direct myocardial effect.

Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 ñ 0.13) caused a sustained increase in renal fractional Na+ excretion (267.9 ñ 36.4 per cent), accompanied by an increase in fractional proximal (113.3 ñ 3.6 per cent) and post-proximal (179.7 ñ 20.2 per cent) Na+ and urinary K+ (163.4 ñ 5.6 per cent) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ñ 4.6 g) and pair-fed (225 ñ 3.6 g) rats compared to the controls (258 ñ 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ñ 0.05 g) compared to the other experimental groups (control, 1.46 ñ 0.05 g; pair-fed, 1.4 ñ 0.05 g). We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

Tissue-specific regulation of IRS-1 in unilaterally nephrectomized rats

Insulin stimulates the tyrosine kinase activity of its receptor, resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-1). IRS-1 is also a substrate for different peptides and growth factors, and a transgenic mouse "knockout" for this protein does not have normal growth. However, the role of IRS-1 in kidney hypertrophy and/or hyperplasia was not investigated. In the present study we investigated IRS-1 protein and tyrosine phosphorylation levels in the remnant kidney after unilateral nephrectomy (UNX) in 6-week-old male Wistar ratas. After insulin stimulation the levels of insulin receptor and IRS-1 tyrosine phosphorylation were reduced to 79 + 5 percent (P<0.005) and 58 + 6 percent (P<0.0001), respectively, of the control (C) levels, in the remnant kidney. It is possible that a circulating factor and/or a local (paracrine) factor playing a role in kidney growth can influence the early steps of insulin action in parallel. To investigate the hypothesis of a circulating factor, we studied the early steps of insulin action in liver and muscle of unilateral nephrectomized rats. There was no change in pp185 tyrosine phosphorylation levels in liver (C 100 + 12 percent vs UNX 89 + 9 percent, NS) and muscle (C 100 + 22 percent vs UNX 91 + 17 percent, NS), and also there was no change in IRS-1 phosphorylation levels in both tissues. These data demonstrate that after unilateral nephrectomy there is a decrease in insulin-induced insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle. It will be of interest to investigate which factors, probably paracrine ones, regulate these early steps of insulin action in the contralateral kidney of unilaterally nephrectomized rats.

Reduced renal sodium excretion in primary hypertensive patients after an oral glucose load

This study was designed to determine urinary sodium excretion in response to an oral glucose load in hypertensive patients. Fifteen hypertensive patients and eighteen normotensive subjects were studied after an overnight fast and for 4 h after the ingestion of 100 g glucose. A subgroup of intreated, nonobese, primary hypertensive patients (five of the 15 hypertensive patients) became hyperinsulinemic (total area under the insulin curve[TAUC]:33,080 + 3349 muU ml(-1) 120 min(-1) in response to an oral glucose load compared to normotensive subjects (TAUC: 3670<13.731<23,693 muU ml(-1) 120 min(-1) or to the other subgroup of normoinsulinemic hypertensive individuals (TAUC:10,221 + 1615 muU ml(-1) 120 min(-1) despite a similar serum glucose concentration in both groups. A significant decrease in renal sodium excretion in the entire hypertensive group (47.1 + 4.7 per cent, P<0.019) compared to the normotensive (20.0 + 10.5 per cent) subjects was also observed during the oral glucose tolerance test. Decreased renal sodium excretion was followed by a transient increase in urinary acid excretion. We speculate that the increase in insulin secretion may be responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+ output and blood pressure in a subgroup of salt-sensitive patients with hypertension. New studies should be designed to identify the precise mechanisms involved in the interaction between hypertension, serum insulin-glucose levels and the magnitude of the renal tubule reabsorption abnormality.

Renal tubular sodium handling determined by lithium clearance in partially hepatectomized rats

Decreased renal sodium excretion was observed 2 to 5 days after a two-thirds hepatectomy (Hx) in male Wistar-Hannover rats (200-300 g; N = 10 per group). This fall occurred after normalization of serum liver enzymes by the second day. Hepatocellular dysfunction was demonstrated by a pronounced and transient increase of about 1150 per cent in plasma alanine aminotransferase (ALT), 500 per cent in aspartate aminotransferase (AST), 250 per cent in alkaline phosphatase (ALP) and in serum direct bilirubin levels, which were about six-fold higher than in sham-operated (SH) animals on the first and second days aft hepatectomy. On the basis of the renal clearance of lithium in partially hepatectomized rats, there was a sustained decrease in fractional sodium excretion between the second (SH: 0.053 ñ 0.008 per cent vs Hx: 0.023 ñ 0.008 per cent) and fifth days (SH: 0.040 ñ 0.006 per cent vs Hx: 0.027 ñ 0.009 per cent) post-hepatectomy. This decrease was accompanied by a rise in the absolute (68 ñ 5.2 mumol min-1 100 g body weight-l) an fractional (85.2 ñ 1.4 per cent) proximal sodium reabsorption rates compared to sham-operated rats (53 ñ 3.5 mumol min-1 100 g body weigh-1 and 80.6 ñ 1.1 per cent), but a return to baseline excretion levels was observed by the tenth experimental day. These changes occurred in the absence of any alterations in creatinine clearance, sodium filtered load, hematocrit and total blood volume. Further studies are required to establish the mechanisms of interaction between renal tubule sodium handling and liver function.

Insulin resistance and myocardial hypertrophy in the attenuated reduction in mean arterial pressure after a glucose load in hypertensive patients

Although long recognized, the vasodilator effect of insulin has been relatively neglected over the last few years. Recent reports have focused on the sympathetic and antinatriuretic actions of this hormone. In the first part of the present study we characterized the reduction in blood pressure after a glucose load in hypertensive patients with and without insulin resistance. fourteen hypertensive Caucasian patients and ten Caucasian controls were submitted to a standard oral glucose tolerance test (OGTT) and intravenous insulin tolerance test (15-min ITT). In the hypertensive patients with insulin resistance the reduction in mean arterial presure (MAP) after a glucose load was blunted (6.7 ñ 1.7 per cent (N = 5)) when compared to insulin-sensitive (12.9 ñ 1.1 per cent (N = 9)) and normal subjects (10.1 ñ 0.8 per cent). IN the second part of the study we investigated whether hypertensive patients with myocardial hypertrophy were more insulin resistant than hypertensive individuals with a normal cardiac mass. The glucose disappearance rate (Kitt) was lower in hypertensive patients with myocardial myocardial hypertensive patients with myocardial hypertrophy (6.0 ñ 1.0 (N = 6)) when compared to hypertensive patients without myocardial hypertrophy (8.2 ñ 1.0 per cent/min (N = 8)), suggesting an association between this organomegaly and insulin resistance. In conclusion, our results suggested that 1) insulin resistance, rather than hyperinsulinemia, acts as a risk factor for the development of hypertension, because of insulin's inability to decrease MAP in this situation, and 2) there is an association between left ventricular hypertrophy and insulin resistance in hypertensive patients

Heterogenous insulin response to an oral glucose load by patients with the indeterminate clinical form of Chagas' disease

This study was designed to investigate the behavior of serum glucose and insulin in response to an oral glucose load in chagasic patients with the indeterminate clinical form of the disease. Sixteen chagasic patients and 28 healthy control subjects were studied after an overnight fast and during 2 h after ingestion of 100 g glucose. There were no significant differences in serum glucose levels before and 2 h after the glucose load between chagasic and control subjects. However, in 8 chagasic patients, the total area under the insulin curve was significantly lower (2976 +/- 448 microU ml-1 120 min-1) than in the control (10123 +/- 995 microU ml-1 120 min-1) and in the remaining chagasic patients (9220 +/- 826 microU ml-1 120 min-1). These results suggest that the hypoinsulinemia of this subgroup of chagasic patients may be secondary to reduced insulin secretion and/or to increased peripheral insulin sensitivity probably related to autonomic dysfunction

Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats

The participation of specific of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). Microinjection of noradrenaline (12.5 to 100.0 nmol/ul) into the LHA promoted a significant decrease in proximal sodium reabsorption (control, 86.5 ñ 1.3; 12.5,81.4 ñ 2.4; 50.0, 75.4 ñ 1.8 and 100.0,77.2 ñ 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 ñ 1.6; 12.5, 18.4 ñ 1.25.0,26.9 ñ 2.9; 50.0,24.1 ñ 2.7; 100.0,22.1 ñ 1.9%) with no significannt changes inm creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/ul. Beyond this concentration, a smaller but progressive increase in fraqctional sodium reabsorption was observed in the post-proximal segment. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area

Male Wistar rats weighing 230-3--g were used to characterize the participation of adrenerg and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 ñ 0.005 to o.019 ñ 0.003 µlmin-1 100g body weight-1) and noradrenaline (Nad) (0.024 ñ 0.005 to 0.025 ñ 0.004 µl min-1 100g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means ñ SEM for ten rats each group. Tubular water measured by lithim clearance demonstrated that LHA stimulation with CCh (2.8 nmol in 1 µl) and Nad (30.0 nmol in µl) leads to a significant reduction in proximal water reabsorption with CCh, 93.3 ñ 2.6 to 85.4 ñ 1.4%; Nad, 92.7 ñ0.9 to 88.6 ñ 1.3%), with a simultaneous and significant incrase in fluid reabsorption along the post-proximal nephrom segments when compared to control (CNa) (CCh, 6.7 ñ 0.7 to 14.5 ñ 1.1%; Nad 8.2 ñ 0.8 to 11.4 ñ 1.6%) These effects are blocked by muscarinic (atropine, 5 nmol in 1 µl) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 µl) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation

Effects of injection of selective adrenergic receptor antagonists into the lateral hypothalamic area on renal function

Studies were underlaken to characterize the participation of specific alpha-1, alpha-2 and beta adrenoceptors of the lateral hypothalamic area *LHA) in the urinary excretion of sodium and potassium. Alpha-1 and alpha-2 IHA receptors were shown to participate in the regulation of renal sodium and potassium excretion. the effects of noradrenaline microinjection (30 nmol in 1 micronl) into the LHA on urinary sodium excretion (UNaV) are blocked by previous injection of the alpha-1 antagonist prazosin (4 nmol in 1 micronl) from 3.22 ñ 0.25 to 0.59 ñ 0.04 micronEq min-1 100g body weigh-1. Pre-injection of yohimbine, an alpha-2 antaghonist (4 nmol in 1 micronl), synergistically potentiated the action of noradrenaline on UNaV (3.22 ñ 0.25 to 4.02 ñ0.27 micronEq min-1 100g body weight-1) and on urinary potassium excretion (UKV) (0.70 ñ 0.08 to 1.15 ñ 0.12 micronEq min-1g body weight-1). The beta-adrenergic blockers metoprolol (100 nmol in 1 micronl) and propranolo (100 nmol in 1 micronl) had no sunergistic or antagonistic action on the sodium excretion fraction, suggesting that neither of these recptors in present in the LHA. Our results indicate that natriuresis occurs even in the absence of changes in glomerular filtration rate and demonstrate an inhibitory natriuretic effect of an alpha-1 blocker (prazosin) injected into the LHA before adrenaline, wile an alpha-2 antagonsit (yohimbine) yielded a potentiating effect (AU)ñ

Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypopthalamic area

Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microng in 1 micronl) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was bloced by prior microinjection of atropine (4 microng/micronl) into the same brain area and was accompanied by an increased soldium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results

Insulin resistance in essential hypertension

To determine the possible existence of a relationship between insulin resistance and sympthetic nervous system activity in essential hypertension, we calculated the double cross index for 14 hypertensive sujects and 14 normotensive subjects submitted to the oral glucose test. Plasma glucose and insulin levels were similar in hypertensive and normotensive subjects. After glucose loading, however, both parameters were significantly higher in hypertensive subjects. Five out of 14 hypertensive patients were hyperinsulinemic. The increase in double cross index following a glucose load was significantly higher in normotensive volunteers than in hyperinsulinemic hypertensive subjects. No change in double cross index was observed in normoinsulinemic hypertensive subjects. Thus, insulin resistance, high blood glucose level, impairment of cardiac response and hyperinsulinemia are present in a significant portion of hypertensive patients. Hyperinsulinemia may contribute to hypertensión by stimulating sympathetic nervous system activity, by influencing the calcium transport across the cell membrane and/or by some other mechanism