The development of a relevant and comprehensive research agenda to improve Hispanic health.

The development of an appropriate research agenda for Hispanics requires progress in three areas: (a) developing an appropriate research infrastructure, (b) increasing the availability of appropriate research instrumentation, and (c) identifying and assigning priority areas. In addition, a Latino health research agenda must identify mechanisms for increasing the number of trained Hispanic researchers and the number of Latino professional staff members at the Department of Health and Human Services. It is recommended that an Office of Hispanic Health be established within the Office of Minority Health at the Department to oversee the implementation of the recommendations made as part of the Surgeon General's National Hispanic Health Initiative.

Renal hemodynamics and urinary concentrating capacity in protein deprivation: role of antidiuretic hormone.

The role of antidiuretic hormone (ADH) in the renal concentration defect and hemodynamic changes in protein malnutrition was evaluated in rats with diabetes insipidus (DI) after 2 weeks of low protein feeding. Free water reabsorptive capacity (TcH2O), glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in the protein deprived rats and in DI rats fed a normal protein diet. The effect of urea supplementation of the low protein diet on renal concentrating capacity was also evaluated. In addition, the renal hemodynamic response to acute administration of ADH was measured and correlated with changes in plasma renin concentration and renal renin content (RRC). Protein deprivation in DI rats resulted in reduced urine osmolality and urea excretion, differences which were reversed by urea supplementation. Protein deprivation did not affect free water reabsorptive capacity but did reduce GFR and RPF. Acute ADH administration significantly increased GFR and RPF in protein-deprived rats; these changes were associated with a reduction in RRC and release. These results suggest that dietary protein restriction does not directly affect the tubular capacity to generate and reabsorb free water. The hemodynamic changes seen in protein deprivation are not mediated by ADH and may be secondary to increased intrarenal angiotensin II.

Functional studies in experimental renal cortical necrosis in the rat.

Necrosis of the outer two-thirds of the cortex (CN) was induced with boiling water in the left kidney of rats. Two days afterward, morphological damage was shown to be limited to the superficial cortex; deep nephron population was well-preserved. Glucose reabsorption under basal and glucose loading conditions, and extraction of p-aminohippurate, used as indices of proximal tubule integrity, were normal in control and experimental kidneys 48 h after cortical necrosis. Basal fractional water and electrolyte excretion did not differ between control and experimental kidneys. Calculated mean single-nephron glomerular filtration rate (GFR) and plasma flow for superficial (SupGFR and SupNPF) and juxtamedullary nephrons (JMGFR and JMPF) were similar to those obtained by micropuncture and Hanssen's technique for SupGFR, and for JMGFR by Hanssen's. Volume expansion led to a 27% increase in calculated SupGFR, but no change in JMGFR. The JMPF increased by 81%, whereas SupNPF increased by only 23%, suggesting that, in this model, GFR of deep nephrons may be independent of plasma flow. The results indicate that deep nephrons retain their functional integrity 48 h after cortical necrosis. After volume expansion fractional excretion of sodium was greater, and fractional water reabsorption less, in CN than in control kidneys. Thus handling of sodium and water by superficial and deep nephrons under basal conditions was similar, but reabsorptive capacity for deep nephrons of CN was lower during volume expansion. The present studies suggest that deep nephrons can maintain relatively normal function in cortical necrosis.

Effects of extracellular volume expansion on plasma renin concentration in rats with diabetes insipidus.

The effect of acute and chronic expansion of the extracellular fluid volume on plasma renin concentration (PRC) was studied in normal Long-Evans rats (LE rats) and in rats with hereditary hypothalamic diabetes insipidus (DI rats). Chronic deoxycorticosterone acetate (DOCA) treatment, combined with a high sodium intake, significantly reduced PRC of both DI and LE rats. PRC of DI rats, however, remained higher than that of LE rats. Acute volume expansion, either alone or with DOCA treatment, also significantly diminished PRC of both DI and LE rats. PRC of untreated and DOCA-treated DI rats again remained significantly higher than that of LE rats after acute volume expansion. These findings suggest that the elevated PRC normally observed in DI rats is not due solely to diminished volume of extracellular fluid. Instead, the absence of ADH per se may directly alter renin secretion or the sensitivity of the granular cell to other stimuli.

Response to isotonic saline infusion after selective renal cortical ablation in the rat.

The response to progressive volume expansion with isotonic saline was studied in sham-operated (CS) rats and in rats with reduced nephron mass after unilateral removal of cortical tissue (CX) or amputation of the kidney poles (NX). Glomerular filtration rate (GFR) in CS kidneys was not statistically different from that in control kidneys. CX and NX kidneys had GFR values markedly lower than control and CS kidneys. CX kidneys had FENa similar to that of control and CS kidneys until very high rates of urine flow were reached (volume expansion greater than 15% of body weight), when it was greater in CX than in CS or control kidneys (25 +/- 14% vs. 11 +/- 2%; p less than 0.05). The same relationship was found between NX kidneys and their controls: FENa only exceeded the values in control kidneys at high rates of urine flow. A defect in free water reabsorption was present in CX when compared to CS and control kidneys, while NX kidneys had TcH2O values which were not different from control kidneys. This different response of CX and NX kidneys suggests that the behavior of CX kidneys cannot be attributed simply to a nonspecific reduction of renal mass. Instead, these results suggest a heterogeneity of nephron function between superficial short-loop nephrons and deep long-loop nephrons primarily with respect to water handling.

Renal Na+-K+-ATPase in weanling and adult spontaneously hypertensive rats.

The interrelationships among plasma renin activity (PRA, ng AI/ml plasma/hr), aldosterone concentration (ng%), and renal Na+-K+-ATPase activity (mumole PO4/mg protein/hr) were studied in 9 weanling normotensive spontaneously hypertensive rats (SHR), 9 adult hypertensive SHR, and 9 weanling and 9 adult normotensive Wistar-Kyoto rats (WKY). All groups were placed on a normal (0.4% sodium) diet. PRA and plasma aldosterone, measured in samples drawn from the ether-anesthetized rat, were higher in weanling SHR (15.2 +/- 2.0, 37 +/- 4.2) than in WKY. PRA measured in samples collected from a separate group of unanesthetized weanling SHR was also greater than in age-matched WKY. In adult SHR, PRA (6.1 +/- 0.9) and plasma aldosterone (20.0 +/- 2.7) were decreased. During the weanling period Na+-K+-ATPase activity in SHR was not only greater than in age-matched WKY but was also increased compared to adult normotensive and hypertensive rats (137 +/- 9 weanling SHR, 89 +/- 7 weanling WKY, 73 +/- 11 adult SHR, 84 +/- 17 adult WKY). Thus, during the weanling period the renin-angiotensin-aldosterone (R-A-A) system and renal Na+-K+-ATPase activity are activated in SHR. The elevation of Na+-K+-ATPase activity may be due to increased aldosterone levels. It was noted, however, that plasma aldosterone was similar in adult WKY and weanling SHR, while Na+-K+-ATPase activity was higher in SHR. These findings involving R-A-A and renal Na+-K+-ATPase activity prior to the elevation of blood pressure suggest that the kidneys may play a role in the initiation of hypertension in SHR.

Effects of endogenous antidiuretic hormone (ADH) on macrophage phagocytosis.

Although several studies have indicated that antidiuretic hormone (ADH) enhances the phagocytic function of the reticuloendothelial system (RES) in shock syndromes, it remains unknown what influence ADH exerts upon the individual phagocytic components of this system. The present investigation was designed to evaluate the effects of endogenous ADH on the phagocytic activity of peritoneal macrophage cells. As a phagocytic stimuli, fluorescent methacrylate microbeads were injected intraperitoneally into Brattleboro (ADH deficient) and normal Long Evans rats in the presence and absence of exogenous ADH. Peritoneal cells were harvested 19-22 hr after the administration of the microbeads and the percent phagocytosis was determined in macrophage cells using a fluorescence-activated cell sorter (FACS II). Our results indicate that the percentage of peritoneal macrophages ingesting the fluorescent methacrylate microbeads was significantly reduced in the absence of ADH (Brattleboro rats: 5.4 +/- 0.6% versus Long Evans rats: 16.8 +/- 2.3%; p less than 0.001). In addition, our data demonstrate that exogenous administration of ADH significantly enhanced macrophage phagocytosis in Brattleboro (14.7 +/- 2.2%) and normal Long Evans (49.6 +/- 4.5%) rats. These data suggest, for the first time, that endogenous ADH might play a modulatory role in the phagocytic activity of a specific component of the RES, namely, the macrophage cell.

The effects of antidiuretic hormone and state of potassium balance on the renin-angiotensin system in rats with diabetes insipidus.

1. The influence of ADH and the state of potassium balance on the renin-angiotensin system was studied in rats with hereditary diabetes insipidus (DI rats). 2. Plasma renin concentration in DI rats was higher than in control Long-Evans rats. 3. Spontaneous reversal of the hypokalaemia normally found in DI rats did not reduce plasma renin concentration (p.r.c.), suggesting that potassium deficiency does not contribute significantly to the elevation of p.r.c. in DI rats. Similarly, a low potassium diet failed to further increase p.r.c. in DI rats. 4. In contrast, the p.r.c. of DI rats was significantly diminished by a high potassium intake both in the presence and absence of ADH. A highly significant inverse correlation was found between p.r.c. and urinary potassium excretion in both ADH-treated and untreated DI rats on low, normal and high potassium diets. 5. Plasma renin concentration was significantly lower in ADH-treated than in untreated DI rats on a high potassium intake, suggesting that the inhibitory effects of ADH and potassium are additive. 6. ADH consistently reduced p.r.c. in DI rats independent of the state of potassium balance. 7. ADH and potassium may inhibit renin secretion via different mechanisms of action.

Renal Na+-K+-ATPase in Okamoto and Dahl hypertensive rats.

Plasma renin activity (PRA, ng AI/ml/hr), plasma aldosterone (PA, ng%) and renal Na+-K+-ATPase (micron m PO 4/mg protein/hr) were measured in tow groups of eight spontaneously hypertensive rats (SHR), two groups of eight Dahl salt hypertensive rats (SS), and their controls (16 normal Wistar and 16 salt-resistant rats). Measurements were made in one group after 2 weeks on a normal (0.48% sodium) and in the other group after 2 weeks on a low (0.01% sodium) sodium diet. After a normal sodium diet, PRA and PA were lower in both groups of hypertensive rats than in control normotensive animals. Renal NA+-K+-ATPase was lower in SS than in controls: in SHR it was not different from control. On a sodium-free diet, SHR exhibited a rise in renal Na+-K+-ATPase but PRA and PA remained low. In contrast, under similar conditions PRA, PA, and renal Na+-K-ATPase increased in SS rats, although to a lesser extent than in SR. These results suggest that under basal conditions and after low salt diet, renal Na+-K+-ATPase activity in SHR behaves as it does in normal rats. However, the changes are independent of PA in SHR. The reduction in PRA and PA in SS suggest volume expansion hypertension. IN SHR, volume expansion is not present, and renal Na+-K+-ATPase is not altered. Enzyme activity is lower in SS than in SHR and control. This suggests that some factor that results from volume expansion may be responsible for inhibition of renal Na+-K+-ATPase.

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition.

Free water clearance curves during saline, mannitol, glucose and urea diuresis in the rat.

1. Free water clearances were measured during infusion of hypotonic saline, glucose, urea, and mannitol in Brattleboro rats. For each solute the free water clearances were plotted using either V or (C(H2O) + C(Na)) as the distal tubular delivery term.2. In all cases the use of (C(H2O) + C(Na)) as distal delivery term yielded a steeper relationship than when V was used. There were no significant differences in the C(H2O) to V relationship when saline, glucose and mannitol was the solute infused. Urea, however, resulted in a curve with a slope significantly less than that for the other solutes.3. When C(H2O) was plotted against (C(H2O) + C(Na)) there was still no significant difference between the slopes of the curves during saline or mannitol infusion. Use of this delivery term, however, resulted in a slope during glucose infusion which was significantly greater than that during saline or mannitol infusion. The slope for urea infusion remained lower than that for any other solute.4. Regardless of the delivery term used, there was no significant difference in the slopes of the curves for awake Wistar and awake Brattleboro rats during mannitol infusion. This indicates that the awake rat is a suitable model for free water clearance studies.5. The results indicate that NaCl and mannitol are both adequate for free water clearance and that (C(H2O) + C(Na)) is a better index of distal delivery than V.