Fluid conservation in athletes: responses to water intake, supine posture, and immersion

The roles of antidiuretic hormone (ADH) and aldosterone in the elicited diuretic responses of trained and untrained men to seated, supine, and head-out water immersed conditions were studied. Volunteers were comprised of groups of six untrained individuals, six trained swimmers, and six trained runners. Each subject underwent three protocols, six hours in a seated position, supine position, or immersion (35 degrees C water). The last two protocols were preceded and followed by 1 h of seated position. After 10 h of fasting, 0.5% body wt of water was drunk. One hour later the trained groups had higher urine osmolalities (P less than 0.05) and urinary excretion rates of ADH (P less than 0.05) and lower urine flow rates (P less than 0.05) than untrained subjects. Throughout the sitting protocol, urinary ADH was also higher in both trained groups (P less than 0.05). Both supine posture and immersion resulted in significant decreases in urinary ADH in the untrained subjects (P less than 0.05) but no changes wer noted in swimmers and only during the second hour of immersion in the runners (P less than 0.05). The natriuresis and kaliuresis were greater during immersion than in the supine position but plasma renin activity, measured only in trained groups, and plasma aldosterone, measured in the untrained group, were decreased similarly with both protocols. The increases in urinary sodium excretion and urine flow rate were lower in trained than untrained subjects during the supine and immersion protocols (P less than 0.05). The data are compatible with an increased osmotic but decreased volume sensitivity of ADH control in trained men.     

Immersion diuresis without expected suppression of vasopressin

To investigate fluid, electrolyte, and plasma vasopressin (PVP) and renin activity (PRA) responses, six men (20-35 yr) were immersed to the neck (NI) in water at 34.5 degrees C for six h after overnight food and fluid restriction. Diuresis was 1,061 +/- 160 (SE) ml/6 h during immersion and water balance was -1,285 +/- 104 ml/6 h. Preimmersion PVP was 0.7 +/- 0.2 pg/ml and increased to 3.0 +/- 0.6 pg/ml (P less than 0.05) at 6 h. PVP was unchanged at 1.2 +/- 0.1 pg/ml in the 6-h seated nonimmersion experiment at 25 degrees C. Plasma volume increased by 7.8 +/- 1.6% (P less than 0.05) at 60 min of NI and decreased thereafter. Serum osmolality was constant (292 +/- 1 mosmol/kg) throughout NI, whereas PRA decreased progressively from 1.9 to 0.5 ng angiotensin I X ml-1 X h-1 (P less than 0.05) at the end of immersion. In spite of moderate thirst just before NI, thirst sensations were attenuated and no water was consumed ad libitum during immersion. These data indicate that PVP is not suppressed when there is no fluid intake during immersion and suggest that the action of factors other than PVP suppression are necessary to explain the mechanism of immersion diuresis.     

Lithium clearance in water immersion-induced natriuresis in humans

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)     

The value of urine osmolality as an index of stress in the ovine fetus

In ovine fetuses, during 100-130 days of gestation, urine osmolalities less than 175 mosmol/kg water were associated with plasma immunoreactive adrenocorticotrophin (ACTH) concentrations below 40 pg/ml in 40/41 samples. In 18/29 fetuses with urine osmolalities greater than 175 mosmol/kg water plasma ACTH was significantly elevated. In 38 samples of fetal blood there was a significant correlation between plasma ADH and ACTH concentrations. By least squares regression the equation to the line was [ACTH] = 5.06 + 3.70 [ADH] (r = 0.62, P less than 0.001). In 50 samples from fetuses of gestational ages 100-140 days, with urine osmolalities of 302 +/- 86 mosmol/kg (mean +/- SD) the blood pH, pO2 and pCO2 values were not significantly different from those in 50 samples from fetuses with urine osmolalities of 125 +/- 22 mosmol/kg. It is proposed that the measurement of fetal urine osmolality provides a good index of fetal stress. A fetus with a urine osmolality less than 175 mosmol/kg is almost invariably in the optimum, unstressed condition.     

Vasopressin inhibits diuresis induced by water immersion in humans.

We tested the hypothesis that 1-desamino-8-D-arginine vasopressin (DDAVP), a V2-receptor agonist, could inhibit the diuresis induced by water immersion in humans. Water and electrolyte excretion, plasma atrial natriuretic factor concentration, and plasma aldosterone concentration were measured initially and after 3 h of water immersion in 13 healthy sodium-replete men given either placebo or 20 micrograms of intranasal DDAVP. Guanosine 3',5'-cyclic monophosphate and urea excretion and urine osmolality were also determined. DDAVP inhibited the diuresis induced by water immersion in men: 758 +/- 168 (SE) ml/3 h in the placebo group vs. 159 +/- 28 ml/3 h in the DDAVP group (P less than 0.05). After 3 h of water immersion, plasma atrial natriuretic factor concentrations were increased from 11 +/- 2 to 20 +/- 4 pg/ml in the placebo group and from 14 +/- 2 to 33 +/- 4 pg/ml in the DDAVP group (P less than 0.05). Plasma aldosterone concentrations were decreased from 98 +/- 18 to 45 +/- 6 pg/ml in the placebo group (P less than 0.05) and from 54 +/- 17 to 25 +/- 5 pg/ml in the DDAVP group (P less than 0.05). Despite these changes in aldosterone and atrial natriuretic factor concentrations, which should increase sodium excretion, DDAVP decreased the natriuresis induced by water immersion in humans: 56 +/- 8 meq Na+/3 h in the placebo group vs. 36 +/- 6 meq Na+/3 h in the DDAVP group (P less than 0.05). DDAVP may be used to prevent the diuresis associated with central redistribution of blood volumes that occur during water immersion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorenal-endocrine responses to head-out immersion at night

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.     

Hormonal regulation of renal sodium and water excretion during normotensive sodium loading in conscious dogs

Saline was infused intravenously for 90 min to normal, sodium-replete conscious dogs at three different rates (6, 20, and 30 micromol x kg(-1) x min(-1)) as hypertonic solutions (HyperLoad-6, HyperLoad-20, and HyperLoad-30, respectively) or as isotonic solutions (IsoLoad-6, IsoLoad-20, and IsoLoad-30, respectively). Mean arterial blood pressure did not change with any infusion of 6 or 20 micromol x kg(-1) x min(-1). During HyperLoad-6, plasma vasopressin increased by 30%, although the increase in plasma osmolality (1.0 mosmol/kg) was insignificant. During HyperLoad-20, plasma ANG II decreased from 14+/-2 to 7+/-2 pg/ml and sodium excretion increased markedly (2.3+/-0.8 to 19+/-8 micromol/min), whereas glomerular filtration rate (GFR) remained constant. IsoLoad-20 decreased plasma ANG II similarly (13+/-3 to 7+/-1 pg/ml) concomitant with an increase in GFR and a smaller increase in sodium excretion (1.9+/-1.0 to 11+/-6 micromol/min). HyperLoad-30 and IsoLoad-30 increased mean arterial blood pressure by 6-7 mm Hg and decreased plasma ANG II to approximately 6 pg/ml, whereas sodium excretion increased to approximately 60 micromol/min. The data demonstrate that, during slow sodium loading, the rate of excretion of sodium may increase 10-fold without changes in mean arterial blood pressure and GFR and suggest that the increase may be mediated by a decrease in plasma ANG II. Furthermore, the vasopressin system may respond to changes in plasma osmolality undetectable by conventional osmometry.     

Effect of head-out immersion on plasma atrial natriuretic factor in man

This study was conducted to examine the role of atrial natriuretic factor (ANF) in the development of diuresis and natriuresis in response to the head-out immersion in 35 degrees C water. Six male subjects were hydrated (0.5% body wt), sat for 1 hr in air (preimmersion), were immersed in water to the neck for 3 hr, and then sat for 1 hr in air (postimmersion). In another series they were similarly hydrated and then sat for 5 hr in air for the time control. Urine and venous blood samples were collected hourly for creatinine and electrolyte measurements. In addition, the concentration of ANF was determined in unextracted plasma by a radioimmunoassay. The pattern of electrolyte excretion was evaluated on the basis of fractional excretion of filtered load. In the time control series, urine flow and fractional excretion of Na and K remained low throughout the 5-hr experimental period. On the other hand, urine flow increased significantly from the preimmersion level of approximately 2 to approximately 7 ml/min during the first hour of immersion (P less than 0.05), after which it decreased to approximately 5 ml/min during the second hour of immersion (P less than 0.05) and to approximately 2 ml/min during the third hour of immersion. Fractional excretion of Na increased continuously from preimmersion level of approximately 1.0 to approximately 1.8% during the second and third hours of immersion (P less than 0.05) and then decreased to 1.2% during the 1-hr postimmersion period. The plasma ANF remained low (approximately 75 pg/ml) during the 5-hr time control period. In the immersion series, plasma ANF increased significantly from the preimmersion level of approximately 80 to approximately 120 pg/ml during the entire 3-hr immersion period and then returned to the preimmersion level during 1 hr postimmersion. These results indicate that the immersion diuresis and natriuresis are indeed associated with the increased ANF release. However, it can not be ascertained from the present study if the increased ANF contributes directly to these renal responses to immersion or in concert with other mediators.     

Sex differences in osmotic regulation of AVP and renal sodium handling.

To determine sex differences in osmoregulation of arginine vasopressin (AVP) and body water, we studied eight men (24 +/- 1 yr) and eight women (29 +/- 2 yr) during 3% NaCl infusion [hypertonic saline infusion (HSI); 120 min, 0.1 ml. kg body wt(-1). min(-1)]. Subjects then drank 15 ml/kg body wt over 30 min followed by 60 min of rest. Women were studied in the early follicular (F; 16.1 +/- 2.8 pg/ml plasma 17beta-estradiol and 0.6 +/- 0.1 ng/ml plasma progesterone) and midluteal (L; 80.6 +/- 11.4 pg/ml plasma 17beta-estradiol and 12.7 +/- 0.7 ng/ml plasma progesterone) menstrual phases. Basal plasma osmolality was higher in F (286 +/- 1 mosmol/kgH(2)O) and in men (289 +/- 1 mosmol/kgH(2)O) compared with L (280 +/- 1 mosmol/kgH(2)O, P < 0.05). Neither menstrual phase nor gender affected basal plasma AVP concentration (P([AVP]); 1.7 +/- 4, 1.9 +/- 0.4, and 2.2 +/- 0.5 pg/ml for F, L, and men, respectively). The plasma osmolality threshold for AVP release was lowest in L (x-intercept, 263 +/- 3 mosmol/kgH(2)O, P < 0.05) compared with F (273 +/- 2 mosmol/kgH(2)O) and men (270 +/- 4 mosmol/kgH(2)O) during HSI. Men had greater P([AVP])-plasma osmolality slopes (i.e., sensitivity) compared with F and L (slopes = 0.14 +/- 0.04, 0.09 +/- 0.01, and 0.24 +/- 0.07 for F, L, and men, respectively, P < 0.05). Despite similar Na+-regulating hormone responses, men excreted less Na+ during HSI (0.7 +/- 0.1, 0.7 +/- 0.1, and 0.5 +/- 0.1 meq/kg body wt for F, L, and men, respectively, P < 0.05). Furthermore, men had greater systolic blood pressure (119 +/- 5, 119 +/- 5, and 132 +/- 3 mmHg for F, L, and men, respectively, P < 0.05) than F and L. Our data indicate greater sensitivity in P([AVP]) response to changes in plasma osmolality as the primary difference between men and women during HSI. In men, this greater sensitivity was associated with an increase in systolic blood pressure and pulse pressure during HSI, most likely due to a shift in the pressure-natriuresis curve.     

The effect of glucocorticoids on the diluting capacity of the kidney of a desert rodent: Gerbillus campestris]

The ability to excrete a water load was studied in Wistar rats and in gerbils (Gerbillus campestris). The rat excreted the entire water load in less than 2 h whereas Gerbillus campestris excreted less than 60% of the water load in 4 h. The gerbils which had received a dose of 15 micrograms/100 g body weight dexamethasone improved their rate of excretion which attained 92 +/- 6% in 2 h 30 min. The antidiuretic hormone (ADH) measured by radioimmunoassay at the time of maximum diuresis was undetectable in rats; in contrast, in gerbils the level of ADH remained relatively high (55.4 +/- 6.7 pg/ml). We conclude that the partial inability of the gerbil's kidney to excrete a water load is due to a high ADH level and probably to a low concentration of glucocorticoids.     

Excitatory amino acids in rostral ventrolateral medulla support blood pressure during water deprivation in rats

Water deprivation is associated with regional increases in sympathetic tone, but whether this is mediated by changes in brain stem regulation of sympathetic activity is unknown. Therefore, this study tested the hypothesis that water deprivation increases excitatory amino acid (EAA) drive of the rostral ventrolateral medulla (RVLM), by determining whether bilateral microinjection of kynurenate (Kyn; 2.7 nmol) into the RVLM decreases arterial pressure more in water-deprived than water-replete rats. Plasma osmolality was increased in 48-h water-deprived rats (313 +/- 1 mosmol/kgH2O; P < 0.05) compared with 24-h water-deprived rats (306 +/- 2 mosmol/kgH2O) and water-replete animals (300 +/- 2 mosmol/kgH2O). Kyn decreased arterial pressure by 28.1 +/- 5.2 mmHg (P < 0.01) in 48-h water-deprived rats but had no effect in water-replete rats (-5.9 +/- 1.3 mmHg). Variable depressor effects were observed in 24-h water-deprived animals (-12.5 +/- 2.4 mmHg, not significant); however, in all rats the Kyn depressor response was strongly correlated to the osmolality level (P < 0.01; r2 = 0.47). The pressor responses to unilateral microinjection of increasing doses (0.1, 0.5, 1.0, and 5.0 nmol) of glutamate were enhanced (P < 0.05) during water deprivation, but the pressor responses to intravenous phenylephrine injection were smaller (P < 0.05). These data suggest that water deprivation increases EAA drive to the RVLM, in part by increasing responsiveness of the RVLM to EAA such as glutamate.     

Effects of oral contraceptives on body fluid regulation.

To test the hypothesis that estrogen reduces the operating point for osmoregulation of arginine vasopressin (AVP), thirst, and body water balance, we studied nine women (25 +/- 1 yr) during 150 min of dehydrating exercise followed by 180 min of ad libitum rehydration. Subjects were tested six different times, during the early-follicular (twice) and midluteal (twice) menstrual phases and after 4 wk of combined [estradiol-norethindrone (progestin), OC E + P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (P(osm)) was lower in the luteal phase (281 +/- 1 mosmol/kgH(2)O, combined means, P < 0.05), OC E + P (281 +/- 1 mosmol/kgH(2)O, P < 0.05), and OC P (282 +/- 1 mosmol/kgH(2)O, P < 0. 05) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, combined means). High plasma estradiol concentration lowered the P(osm) threshold for AVP release during the luteal phase and during OC E + P [x-intercepts, 282 +/- 2, 278 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O, for follicular, luteal (combined means), OC E + P, and OC P, respectively; P < 0.05, luteal phase and OC E + P vs. follicular phase] during exercise dehydration, and 17beta-estradiol administration lowered the P(osm) threshold for thirst stimulation [x-intercepts, 280 +/- 2, 279 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O for follicular, luteal, OC E + P, and OC P, respectively; P < 0.05, OC E + P vs. follicular phase], without affecting body fluid balance. When plasma 17beta-estradiol concentration was high, P(osm) was low throughout rest, exercise, and rehydration, but plasma arginine vasopressin concentration, thirst, and body fluid retention were unchanged, indicating a lowering of the osmotic operating point for body fluid regulation.     

Estrogen effects on osmotic regulation of AVP and fluid balance

To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP) and body fluids, we suppressed endogenous estrogen and progesterone using the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n = 9, 25 +/- 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n = 6, 26 +/- 3). During GnRHa alone and with hormone treatment, we compared AVP and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml. min(-1). kg body wt(-1)), drinking (30 min, 15 ml/kg body wt), and recovery (60 min of seated rest). Plasma [E(2)] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P(4)] increased from 0.6 to 5.7 ng/ml during E/P and was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced osmotic AVP release threshold (275 +/- 4 to 271 +/- 4 mosmol/kg, P < 0.05), and E/P reduced the AVP increase in response during HSI (6.0 +/- 1.3 to 4.2 +/- 0.6 pg/ml at the end of HSI), but free water clearance was unaffected in either group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during E (0.8 +/- 0.1 vs. 1.2 +/- 0.2 ng ANG I. ml(-1). h(-1)) but not after HSI or recovery. PRA was greater than GnRHa during E/P at baseline (1.1 +/- 0.2 vs. 2.5 +/- 0.6) and after HSI (0.6 +/- 0.1 vs. 1.1 +/- 1.1) and recovery (0.5 +/- 0.1 vs. 1.3 +/- 0.2 ng ANG I. ml(-1). h(-1)). Baseline fractional excretion of sodium was unaffected by E or E/P but was attenuated by the end of recovery for both E (3.3 +/- 0.6 vs. 2.4 +/- 0.4%) and E/P (2.8 +/- 0.4 vs 1.7 +/- 0.4%, GnRHa alone and with hormone treatment, respectively). Fluid retention increased with both hormone treatments. Renal sensitivity to AVP may be lower during E due to intrarenal effects on water and sodium excretion. E/P increased sodium retention and renin-angiotensin-aldosterone stimulation.     

Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.     

Role of renal prostaglandins in the fall in urine osmolality after papillary micropuncture

The effect of micropuncture of the renal papilla through an intact ureter on urinary concentrating ability of rats was examined. Micropuncture of the renal papilla caused a fall in urine osmolality in the punctured kidney from 1718 +/- 106 to 1035 +/- 79 mosmol/kg X H2O. In order to investigate the role of renal prostaglandins in this process, PGE2 excretion was measured and found to increase from 63.4 +/- 14.0 to 205.5 +/- 57.1 pg/min. Urine osmolality and PGE2 excretion from the contralateral kidney were not significantly altered. In animals given meclofenamate (2 mg/kg X hr), renal PGE2 excretion was reduced to 22.3 +/- 5.1 pg/min prior to micropuncture and it remained low at 8.9 +/- 1.8 pg/min after papillary micropuncture. Meclofenamate also blocked the fall in urine osmolality caused by micropuncture of the renal papilla, with urine osmolality averaging 1940 +/- 122 before and 1782 +/- 96 mosmol/kg X H2O after the micropuncture. These results indicated that papillary micropuncture through an intact ureter increased renal PGE2 excretion and that a rise in renal production of PGE2 or some other prostanoid is associated with a fall in urine concentrating ability.     

Free fatty acid availability and temperature regulation in cold water

The purpose of this study was to investigate whether a reduced availability of plasma free fatty acids (FFA) would impair human temperature regulation during cold exposure. Seven seminude male subjects were immersed on two occasions in 18 degrees C water for 90 min or until their rectal temperature (Tre) decreased to 35.5 degrees C. The immersion occurred after 2 h of intermittent oral ingestion of either nicotinic acid (NIC) or a placebo (PLAC). Plasma FFA levels immediately before the immersion were significantly lower in NIC (87 +/- 15 mumol/l) than in PLAC (655 +/- 116 mumol/l, P less than 0.05). Although FFA levels increased by 73% in NIC during the immersion (P less than 0.05), they remained significantly lower than in PLAC (151 +/- 19 vs. 716 +/- 74 mumol/l, P less than 0.05) throughout the immersion. Muscle glycogen concentrations in the vastus lateralis decreased after cold water immersion in both trials (P less than 0.05), but the rate of glycogen utilization was similar, averaging 1.00 +/- 0.27 mmol glucose unit.kg dry muscle-1.min-1). Plasma glucose levels were significantly reduced after immersion in both trials (P less than 0.05), this decrease being greater in NIC (1.3 +/- 0.2 mmol/l) than in PLAC (0.7 +/- 0.1 mmol/l, P less than 0.05). O2 uptake increased to 3.8 +/- 0.3 times preimmersion values in both trials (P less than 0.05). Mean respiratory exchange ratio (RER) immediately before the immersion was greater in NIC (0.87 +/- 0.02) than in PLAC (0.77 +/- 0.01, P less than 0.05). Cold exposure increased RER in PLAC but not in NIC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Attenuation of vasopressin-induced antidiuresis in poorly controlled type 2 diabetes

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.     

Effects of calcitonin gene-related peptide on renal blood flow in the rat

The effects of alpha-rat calcitonin gene-related peptide (alpha-rCGRP) on systemic and renal hemodynamics and on renal electrolyte excretion were examined in normal anesthetized rats. In one group of rats (n = 7), infusions of alpha-rCGRP at doses of 10, 50, 100, and 500 ng/kg/min for 15 min each produced dose-related and significant decreases in mean arterial pressure from a control of 130 +/- 3 mm Hg to a maximal depressor response of 91 +/- 2 mm Hg. During the first three doses of alpha-rCGRP, renal blood flow progressively and significantly increased from a control of 5.0 +/- 0.3 ml/min to a peak level of 6.3 +/- 0.3 ml/min achieved during the 100 ng/kg/min infusion. With the highest infusion rate of 500 ng/kg/min, renal blood flow fell below the control level to 4.5 +/- 0.2 ml/min (P less than 0.05). The responses in renal blood flow and mean arterial pressure were associated with reductions in renal vascular resistance. After cessation of alpha-rCGRP infusions, arterial pressure, renal blood flow, and renal vascular resistance gradually returned toward the baseline values. In another group of rats (n = 9), infusion of alpha-rCGRP for 30 min at 100 ng/kg/min produced a significant reduction in urinary sodium excretion from 0.28 +/- 0.06 to 0.14 +/- 0.5 muEq/min (P less than 0.05). Urine flow and urinary potassium excretion also appeared to decrease, but the changes were not significantly different (P greater than 0.05) from their respective baselines. These results demonstrate that alpha-rCGRP is a potent and reversible hypotensive and renal vasodilatory agent in the anesthetized rat. The data also suggest that alpha-rCGRP may have significant effects on the excretory function of the kidney.     

Effects of muscle glycogen and plasma FFA availability on human metabolic responses in cold water.

The purpose of this study was to investigate whether simultaneous alterations in the availability of plasma free fatty acids and muscle glycogen would impair the maintenance of thermal balance during cold water immersion in humans. Eight seminude subjects were immersed on two occasions in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Each immersion followed 2.5 days of a specific dietary and exercise regimen designed to elicit low (LOW) or high glycogen levels (HIGH) in large skeletal muscle groups. Nicotinic acid (1.6 mg/kg) was administered for 2 h before and during immersion to inhibit white adipose tissue lipolysis. Biopsies from the vastus lateralis showed that the glycogen concentration before the immersion was significantly lower in LOW than in HIGH (223 +/- 19 vs. 473 +/- 24 mmol glucose units/kg dry muscle). However, the mean rates of glycogen utilization were not significantly different between trials (LOW 0.62 +/- 0.14 vs. HIGH 0.88 +/- 0.15 mmol glucose units.kg-1.min-1). Nicotinic acid dramatically reduced plasma free fatty acid levels in both trials, averaging 127 +/- 21 mumol/l immediately before the immersion. Cold water immersion did not significantly alter those levels. Plasma glucose levels were significantly reduced after cold water immersion to a similar extent in both trials (18 +/- 4%). Mean respiratory exchange ratio at rest and during immersion was greater in HIGH than LOW, whereas there were no intertrial differences in O2 uptake. The calculated average metabolic heat production during immersion tended to be lower (P = 0.054) in LOW than in HIGH (15.3 +/- 1.9 vs. 17.5 +/- 1.9 kJ/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of atrial natriuretic peptide and urinary cGMP in the natriuretic and diuretic response to central hypervolemia in normal human subjects

The response of plasma atrial natriuretic peptide (ANP) and urinary cGMP excretion to central hypervolemia induced by water immersion was assessed twice in five healthy male subjects, once while immersed in water to the neck for 3 h and again on a control day. Plasma ANP and urinary cGMP were measured by radioimmunoassay. Compared with the control day, overall change in plasma ANP on the immersion day was significant (p less than 0.05). In response to water immersion, plasma ANP increased from a base-line level of 13.2 +/- 3.1 (mean +/- SEM) to 24.2 +/- 5.5 pg/mL by 0.5 h of immersion and was sustained at that level throughout the immersion period. Plasma ANP returned to the base-line level at 1 h postimmersion. Urinary cGMP excretion increased significantly by 1 h of immersion and was sustained at that level throughout water immersion and 1 h postimmersion (p less than 0.05). During water immersion urine flow, urinary sodium and potassium excretion, free water clearance, and osmolar clearance increased while plasma renin activity, serum aldosterone, and blood pressure fell; all changes were significant (p less than 0.05). Creatinine clearance and hematocrit did not show any significant changes. These data suggest that an increase in plasma ANP may contribute to the natriuretic and diuretic response to central hypervolemia, and that the measurement of urinary cGMP may be a valuable marker of ANP biological responsiveness.