Tunicamycin blocks the emergence and maintenance of insulin receptors on mitogen-activated human T lymphocytes

Treatment of phytohemagglutinin (PHA) activated human T lymphocytes with tunicamycin, an antibiotic that specifically inhibits asparagine-linked N-glycosylation of proteins, totally blocked the normal emergence of insulin receptors on these lymphocytes and their cellular proliferation during culture in a dose-dependent manner. Carbohydrate incorporation into protein was inhibited 82% by 0.5 μg/mL while leucine incorporation was unaffected. Tunicamycin exposure of activated T lymphocytes, which had acquired insulin receptors during culture, reduced cellular insulin binding by 35% to 84% and reduced PHA binding to 40% of control levels within 24 hours. Scatchard analysis revealed decreases in insulin binding capacity but not affinity. Similar treatment with cycloheximide only decreased insulin binding by 12%. These findings suggest N-glycosylation of proteins is a necessary biochemical event (1) for the emergence and maintenance of insulin receptors on mitogen activated T lymphocytes, and (2) for mitogen activated T lymphocytes to undergo cell division.     

Interactions of insulin with bovine endothelium

Bovine endothelial cells have been isolated from pulmonary and systemic vessels and grown in culture as primary, passaged and passaged cloned-strains. The cultures were shown to be endothelial in nature on the basis of several endothelial-specific and endothelial-associated traits. Endothelial cells from all sources had specific receptors for insulin in primary culture and after serial passage. Endothelial cells derived from pulmonary arteries and aortas bound 2.5 times more insulin than cells derived from the pulmonary vein. Each endothelial cell type maintained a specific complement of receptors through at least 25 passages in vitro. Coupled with previous findings of insulin receptors on endothelial cells from human umbilical vessels, these data suggest that insulin receptors may be an intrinsic component of all vascular endothelium.     

Changes in bone and serum minerals after parathyroidectomy and their prevention by portacaval shunt

The effect of portacaval shunt and parathyroidectomy on the concentration of calcium, magnesium, phosphate and hydroxyproline in the bone and the concentration of the three minerals in the serum has been studied in the growing rat. Parathyroidectomy produced a decreased net bone resorption as evidenced by higher concentrations of calcium, magnesium and phosphate; and a reduced net matrix formation, as evidenced by lower concentrations of hydroxyproline. Portacaval shunt, when performed with parathyroidectomy, prevented the development of these changes and produced “normal” concentrations of most of those elements, comparable to their concentrations in the control animals. The changes in serum calcium and magnesium produced by parathyroidectomy were prevented when portacaval shunt was performed in conjunction with the former procedure. Portacaval shunt alone produced no significant changes except for hypophosphatemia. This hypophosphatemia is speculated to have stimulated the production of 1,25-(OH)₂D₃ in the kidney, which in turn produced those observed effects of portacaval shunt in the parathyroidectomized rat.     

Magnesium balance and distribution during total parenteral nutrition: effect of calcium additives

Homeostatic alterations and derangements in magnesium (and phosphate) metabolism may occur during total parenteral nutrition (TPN) and may be influenced by the amounts of calcium supplied daily. We tested these possibilities in previously fasted or nonfasted animals receiving TPN with variable amounts of calcium. Large calcium additives (90 mg/d) produced hypomagnesemia in nonfasted animals and increased the degree of hypomagnesemia observed in some of the fasted groups. Bone and muscle magnesium were occasionally altered, by high-calcium additives. Urine magnesium was increased, metabolism may have been dependent upon the amount of calcium added and magnesium supplied in TPN. Some of the derangements may have been dependent upon the state of fasting (and resultant phosphate-depletion syndrome).     

Placental transfer of aspartate and its metabolites in the primate.

The placental transfer of aspartate was tested in pregnant monkeys infused maternally with sodium aspartate. In five animals infused at 100 mg/kg/hr, maternal plasma aspartate levels increased from 0.36 ± 0.19 to 80.2 ± 11.5 μmole/dl (mean ± SD). However, fetal plasma aspartate levels increased only slightly from 0.42 ± 0.31 to 0.98 ± 0.24 μmole/dl (p = 0.02). Erythrocyte aspartate levels were unchanged in both fetal and maternal circulation. In two animals infused at 200 mg/kg/hr, maternal plasma aspartate levels increased from 0.28 and 0.31 μmole/dl to values of 141 and 237 μmole/dl, respectively. This increase produced a significant (p = 0.001) increase in fetal plasma aspartate levels from 0.53 and 0.67 to 3.3 and 4.5 μmole/dl, respectively. Maternal plasma aspartate levels in two animals infused at 400 mg/kg/hr increased from 0.5 and 0.7 μmole/dl to 400 and 750 μmole/dl, respectively, at the end of the infusion. Fetal plasma aspartate levels increased from 0.21 and 0.25 μmole/dl to 60 and 92 μmole/dl, respectively. Maternal aspartate infusion at each level increased maternal, but not fetal, plasma taurine levels. The increase in maternal taurine levels was not in proportion to the dose of aspartate infused. Aspartate metabolites, glucose, and lactate were readily transferred across the placenta. The data indicate that aspartate, like glutamate but unlike most amino acids, is not concentrated toward the fetal circulation in the pregnant primate, and suggest that a barrier to aspartate transfer exists unless maternal plasma levels are grossly elevated.     

Free and total insulin integrated concentrations in insulin dependent diabetes

Studies of the 24 hr insulin concentration profiles in diabetic subjects on chronic exogenous insulin have been hampered by the presence of endogenous anti-insulin antibody, which gives spurious estimates of radioimmunoassayable insulin concentrations. The introduction of polyethylene glycol precipitation of endogenous antibody has allowed development of reliable assays for determiniation of free and total insulin concentration in subjects on insulin therapy. This article reports our observations of plasma free and total insulin concentration in 50 Type I and Type II ambulatory insulin dependent diabetics, utilizing a continuous 24 hr blood withdrawal technique. In response to exogenous insulin, study subjects had marked elevations in insulin concentrations compared to controls. Mean free insulin integrated concentration was 3.5-fold higher in diabetics than nondiabetics. Mean total insulin integrated concentration was 868 μU/ml, more than 20 times in excess of total insulin concentration in nondiabetics. There was a wide range among diabetics in the percentage of total insulin in the free insulin fraction. Neither free nor total insulin integrated concentration correlated with dose of exogenous insulin. Free and total insulin concentration profiles showed a limited range of variation in insulin concentration during the 24 hr of study, no subject having a profile that mimicked that observed in nondiabetic subjects. Glucose integrated concentration showed no correlation with free insulin integrated concentration, however, it did correlate inversely with the percentage of total insulin in the free insulin fraction. These data emphasize the difficulty in establishing normal patterns of insulin among diabetic subjects on conventional subcutaneous insulin therapy.     

The transport and metabolism of L-proline-14C in the rat in vivo

The physiologic disposition, metabolic fate, and renal clearance of intravenously injected 14C-L-proline was determined in the rat. The disappearance of radioactivity from plasma occurred with a biphasic curve, the initial high levels reaching a nadir about 30 min after injection with subsequent increasing amounts of radioactivity. Examination of the 14C components in plasma revealed that 14C-proline disappeared rapidly during the first 30 min. At this time, the labeling of circulating plasma proteins ensued and continued to increase during the following 45 min of observations. Plasma glucose became labeled 10 min after injection and, thereafter, increased its 14C content. The extensive labeling of plasma proteins and glucose accounted for the increasing 14C found in plasma 30 min after injection. The course of radioactive labeling of brain, kidney, diaphragm, and liver was assessed. The greatest number of cpm/mg of tissue was found in the kidney. Determination of the distribution ratio, the ratio of cpm/ml intracellular nonprotein 14C to that in plasma in kidney revealed a peak of 3.9 within 15 min, a value comparable to that found in vitro. Twelve percent of the administered radioactivity was excreted as 14CO2 within 180 min. The oxidation was inhibited by known transport and metabolic inhibitors, the greatest effect observed with hydroxyproline, followed in order by thioproline, 3,4-dihydroproline, and glycine. The fractional urinary excretion of proline, Cproline/Cinulin, was determined and found to be 1% or less. This was increased by inhibitors, the greatest effect due to hydroxyproline followed in order by dehydroproline and glycine, a result similar to the observed extent of inhibition of proline oxidation to 14C O2. The physiologic disposition of proline was not altered by ligation of the renal vasculature.     

Inhibition of glucose-induced insulin secretion by intravenous colchicine in man

Colchicine, a pharmacologic agent commonly used to treat acute gout is a potent microtubular inhibiting agent in vitro. Acute and chronic colchicine administration was found by others to significantly suppress glucose-induced biphasic insulin (IRI) secretion and to markedly impair glucose disappearance rate in the intact rat. It has also been shown to inhibit the second phase of glucose-induced IRI release in vitro. However, both studies were performed using colchicine doses that would be lethal to man. We studied the effects of a commonly used and safe dose of colchicine—3 mg IV—in paired experiments in 12 nondiabetic human subjects. We used a glucose infusion previously determined to give maximal biphasic IRI release and measured IRI for a 75-min period 30 min after either saline control or colchicine. Differences in IRI release between the control and colchicine experiments were examined for the total 75-min glucose infusion as well as for the acute (0–20 min) and late (30–75 min) phases. Colchicine concentration by radioimmunoassay varied from 1.8 μg/dl at the beginning of glucose infusion to 1.1 μg/dl at the end of infusion. Pretreatment with colchicine resulted in decreased IRI release in the first phase, with a mean decrease of 113 ± 44 μU/time (p < 0.05), in the second phase a decrease of 308 ± 124 μU/time (p < 0.05) and a mean decreased IRI release for the total 75-min glucose infusion of 438 ± 142 μU/time (p < 0.02). Thus, we can conclude that a therapeutic dose of colchicine can significantly inhibit biphasic glucose-induced IRI release in man. Although the mechanism is not certain it is possible that this phenomenon is secondary to microtubular disruption.     

Relationship between insulin resistance,insulin secretion,very low density lipoprotein kinetics,and plasma triglyceride levels in normotriglyceridemic man

We have previously postulated that resistance to insulin-mediated glucose uptake was the basic metabolic abnormality in patients with endogenous hypertriglyceridemia. In this situation, glucose tolerance would tend to deteriorate, and could only be maintained by the increased secretion of insulin. Although the ensuing hyperinsulinemia might prevent the development of glucose intolerance, we suggested that it would also lead to increased hepatic very low density (VLDL) triglyceride (TG) synthesis and secretion. In the current study we have quantified these four metabolic variables in 16 nonobese human subjects with plasma TG concentrations < 175 mg/dl. The results demonstrate the following degree of correlation: insulin resistance

insulin response to food

VLDL-TG secretion rate

plasma TG concentration. These data indicate that nonobese subjects with normal TG levels have the same relationship between degree of insulin sensitivity, insulin response to food, VLDL-TG secretion, and TG concentration previously described in patients with endogenous hypertriglyceridemia.     

Effects of prostaglandin H2, prostaglandin E2, and arachidonic acid on parathyroid hormone and antidiuretic hormone activation of rat kidney adenylate cyclase

These experiments examine interactions of arachidonic acid; the substrate for prostaglandin cyclooxygenase, prostaglandin (PG)H₂, a key endoperoxide intermediate in prostaglandin synthesis; and prostaglandin (PG)E₂, an important prostaglandin produced within the kidney; with adenylate cyclase activity in renal cortex, outer medulla, and inner medulla. In addition, the effects of arachidonic acid, PGH₂, and PGE₂ on parathyroid hormone (PTH) activation of adenylate cyclase in cortex, and of antidiuretic hormone (ADH) activation of that enzyme in outer and inner medulla are examined. Arachidonic acid elicited a concentration-dependent inhibition of basal and PTH-stimulated adenylate cyclase activity in renal cortex. Concentration-dependent inhibition by arachidonic acid of basal and ADH-stimulated adenylate cyclase activity was observed in outer and inner medulla. PGH₂ inhibited basal activity in all three areas of the kidney. There was also inhibition by PGH₂ of medullary ADH and cortical PTH stimulation. PGE₂ stimulated adenylate cyclase in all three areas. PGE₂ had no effect upon PTH stimulation in cortex and was additive with ADH in outer and inner medulla. PGE₂ stimulation was inhibited by arachidonic acid, and this inhibition seemed competitive. Inhibition by both arachidonic acid and PGH₂ was not destructive. Experiments with [1-¹⁴C]arachidonic acid and indomethacin suggest that the inhibition by arachidonic acid was actually mediated by arachidonic acid and not a metabolite. Both PGH₂ and arachidonic acid inhibition was independent of phosphodiesterase. This activation by product, PGE₂, and inhibition by its precursors, arachidonic acid and PGH₂, provide a possible mechanism by which the prostaglandin system could modulate adenylate cyclase responsiveness to hormonal activation.     

Effect of meal components on peripheral and portal plasma glutamate levels in young pigs administered large doses of monosodium-L-glutamate

Mean peak plasma glutamate concentrations and area under the plasma glutamate concentration-time curve are much lower in adult humans ingesting monosodium L-glutamate (MSG) in formula than in water. The present study investigated the effects of individual meal components on portal and vena caval plasma glutamate concentration in young pigs administered MSG. Portal vein catheters and gastrojejunal tubes were placed in four young male pigs, and the animals were allowed to recover. Each animal was then administered four water solutions providing 500 mg/kg body weight MSG in a Latin square design. One solution provided only MSG; the second provided MSG and 1 g/kg body weight metabolizable carbohydrate (partially hydrolyzed corn starch); the third provided MSG and 1 g/kg body weight nonmetabolizable carbohydrate (beta-cellobiose); and the fourth provided MSG and 0.4 g/kg body weight of an amino acid mixture (Aminosyn, Abbott Laboratories, North Chicago, Ill). Mean peak plasma glutamate concentration and area under the plasma glutamate concentration-time curve were significantly lower (P less than 0.05) in both portal and vena caval blood when MSG was administered with metabolizable carbohydrate than when administered in water. Simultaneous ingestion of MSG with nonmetabolizable carbohydrate (beta-cellobiose) or amino acids had no significant effect on either mean peak portal or vena caval plasma glutamate concentration or area under the plasma glutamate concentration-time curves when compared to values observed when MSG was administered alone. The data suggest that metabolizable carbohydrate is the meal component affecting plasma glutamate concentration.     

Hypolipidemic effects of high-carbohydrate, high-fiber diets

Serial measurements of serum cholesterol and triglyceride (TG) concentrations were performed in diabetic men fed high-carbohydrate, high-fiber (HCF) as well as high-carbohydrate, low-fiber (HCLF) diets. Fourteen lean men were first fed control diets for 1 wk and then fed weight-maintaining HCF diets (70% carbohydrate) that were restricted in fat and cholesterol. Average insulin doses dropped from 27 U/day on control diets to 12 U/day on HCF diets and fasting plasma glucose values were 26 mg/dl lower on HCF diets. On HCF diets, serum cholesterol values were lower by 32% (64 mg/dl, p < 0.001) than values on control diets. Fasting serum TG values were slightly lower on HCF diets but average postprandial TG values were significantly lower (p < 0.001) on HCF diets than on control diets. In another study, 11 men were fed two weight-maintaining 70% carbohydrate diets in an alternating sequence; one diet was high in plant fiber (HCF) and the other was low in plant fiber (HCLF). Insulin doses averaged 20 U/day on control diets and fell to 11 U/day (p < 0.01) on HCF diets or 12 U/day (p < 0.01) on HCLF diets. Fasting serum TG values were similar on the control and HCF diets; on HCLF diets fasting serum TG values were higher by 28% (37 mg/dl) than values on control diets (p < 0.01). Incorporation of generous amounts of plant fiber into the diet prevented the hypertriglyceridemic response to these high-carbohdrate diets. These studies also indicate that dietary maneuvers can be very effective in lowering serum cholesterol values in patients with diabetes mellitus.     

Urinary excretion of desmosine in patients with severe burns

Urinary excretion of total desmosine was measured by a radioimmunoassay in severely burned adult males, as well as in normal adult males. Total urinary desmosine was significantly elevated in all the samples in the burned patients, who had injuries involving more than 19% of total body surface area. The values of 24-hr urinary desmosine for the burned patients ranged from 250–1,411 nmoles, as compared with 82–142 nmoles for normal controls. These were equivalent to 14–78 mg of elastin degraded for the burned patients and 5–8 mg for normal controls. Urinary desmosine values expressed as nmoles per g of creatinine were also higher than the corresponding normal values, ranging from 110–768 nmoles versus 63 ± 6 nmoles for normal controls. Urinary excretion of total hydroxyproline in the burned patients was also higher than in normal controls, ranging from 56–471 mg per 24 hrs, or 36 to 413 mg per g of creatinine, vs. 31 ± 6 mg per 24 hr, or 23 ± 2 mg per g of creatinine, in burned patients and normal controls, respectively. These values of hydroxyproline were equivalent to 413–3,623 mg of collagen and 238 mg of collagen, respectively. In the burned patients, both urinary desmosine and hydroxyproline values were elevated from day 1 post-burn, and reached peak levels in days 2–12, declining thereafter but remaining higher than values for normal controls through day 60. The metabolism of elastin and collagen in skin of burned patients was probably highly accelerated for a long time, at least through day 60 post-burn.     

Triglyceride-integrated concentration: relationship to insulin-integrated concentration.

The relationship between plasma insulin and plasma triglyceride concentrations in response to diet alterations was studied in eight healthy adult male subjects. Four isocaloric formula diets, providing either 45% or 65% of total energy from carbohydrate and, using either sucrose or corn syrup as the carbohydrate source, were ingested for 10 days in a Latin Square sequence. Plasma triglyceride and insulin responses to diet alterations were assessed in blood samples after overnight fast and in samples obtained by a 24-hr continuous withdrawal technique, the mean concentrations of plasma insulin and plasma triglyceride during the 24-hr period of study were designated as the insulin-integrated concentration and triglyceride-integrated concentration respectively. Mean insulin integrated concentrations were 45% to 57% higher and mean triglyceride integrated concentrations 19% to 27% lower during ingestion of analogous diets containing sucrose. Increases in the percentage of total energy supplied as carbohydrate did not significantly change the insulin integrated concentration. Seven of the eight subjects had higher insulin-integrated concentrations associated with lower triglyceride-integrated concentrations during the four diet periods (r ranged from −.536 to −.777), while one subject had a positive correlation (+.324). There was a statistically significant (p < .01) inverse relationship between the mean insulin- and triglyceride-integrated concentrations during the four diet periods.     

Effect of palmitate on hepatic biosynthetic functions at hyperthermic temperatures

Livers of fasted rats were perfused for 80 min at 37°–43°C, supplemented with lactate, NH₄Cl, and ornithine in the presence or absence of palmitate. Hepatic functional integrity was maintained from 37° to 42°C as assessed by gluconeogenesis, ureogenesis, and O₂ consumption. Between 42° and 43°C a sharp decline in biosynthetic function occurred. The ratio of lactate disappearance to glucose formation increased progressively with increasing temperature when compared with the ratio obtained at 37°C. Exogenous palmitate significantly decreased the ratio of lactate disappearance to glucose formation at 43°C. Furthermore, palmitate attenuated the detrimental effects of hyperthermia on gluconeogenesis, ureogenesis, and O₂ consumption found in the absence of palmitate. The 3-hydroxybutyrate/acetoacetate ratio progressively decreased as the liver temperature was increased in the presence or absence of palmitate, indicating a more oxidized mitochondrial redox state. Palmitate significantly increased the 3-hydroxybutyrate/acetoacetate ratio in the presence of gluconeogenic and ureogenic substrates at all temperatures examined. The data suggest that provision of fatty acid has a protective effect in thermally stressed liver. Moreover, palmitate may substitute for the increased energy requirements of the hyperthermic state.     

Relationship between calcium stimulation of cyclic GMP and lipid peroxidation in the rat kidney: evidence for involvement of calmodulin and separate pathways of peroxidation in cortex versus inner medulla

The relationship between Ca²⁺ stimulation of renal cGMP accumulation, release of endogenous arachidonic acid (AA) from lipid stores, lipid peroxidation and prostaglandin (PG) synthesis were examined in rat renal cortex and inner medulla. In slice incubates of each tissue, increases in slice cGMP induced by Ca²⁺ plus ionophore A23187 were preceded by or occurred concurrently with Ca²⁺ induced increases in (1) release of [¹⁴C] AA from prelabeled lipid stores, (2) lipid peroxidation, as monitored by accumulation of malondialdehyde (MDA) in the media, and (3) inner medullary slice PGE content. Ca²⁺ induced increases in cGMP, MDA and PGE required O₂. Exogenous AA also increased MDA, PGE and cGMP in the presence but not in the absence of O₂. In inner medulla, the cyclooxygenase inhibitors indomethacin or meclofenamate suppressed or abolished the actions of Ca²⁺, Ca²⁺ plus A23187 or exogenous AA to increase MDA, PGE and cGMP, thus implicating products of the prostaglandin synthetic pathway as potential mediators of Ca²⁺ effects on cGMP in this tissue. By contrast, in renal cortex, the cyclooxygenase inhibitors did not alter Ca²⁺, A23187 or AA induced increases in MDA or cGMP. However, preformed AA hydroperoxide significantly stimulated soluble and particulate guanylate cyclase activities from both regions of the kidney, suggesting that oxygenation of AA by the lipoxygenase pathway could result in generation of products capable of enhancing cGMP accumulation in cortex. Trifluoperazine (TFP), a phenothiazine that binds to and inhibits many of the biologic actions of the Ca²⁺-calmodulin complex, suppressed increases in [¹⁴C] AA release, MDA and cGMP induced by Ca²⁺ or Ca²⁺ plus A23187 in both cortex and medulla. By contrast, TFP did not alter increases in MDA or cGMP in response to exogenous AA or the increase in cGMP induced by nitroprusside. Promethazine, a phenothiazine which binds poorly to Ca²⁺-calmodulin, had no effect on Ca²⁺ induced increases in MDA or cGMP in cortex or medulla, TFP, but not promethazine, also suppressed Ca²⁺ induced increases in acyl hydrolase activities in the 100,000 xg particulate fractions from cortex and medulla. Reduction of the endogenous calmodulin-like activity of particulate fractions from inner medulla by extraction with EGTA was associated with loss of Ca²⁺ responsive acyl hydrolase activity. Ca²⁺-responsiveness was restored by addition of purified exogenous calmodulin. The data are consistent with the proposal that Ca²⁺ induced increases in cGMP involve (1) Ca²⁺ stimulation of Ca²⁺-calmodulin responsive acyl hydrolase activity with liberation of AA from lipid stores, and (2) oxygenation of AA by cyclooxygenase (medulla) or lipoxygenase (cortex) pathways to products which activate guanylate cyclase.     

Brown adipose tissue metabolism in hypothalamic-obese rats

Studies were performed to evaluate the metabolic changes of brown adipose tissue (BAT) in rats with hypothalamic obesity (VMNL). In vitro 14C-palmitate oxidation and incorporation into triglycerides were similar in VMNL and control rats. However, protein and fatty acid content and incorporation of 14C-palmitate into phospholipid were significantly less in both hyperphagic and normophagic VMNL rats. In order to assess in vivo BAT lipogenesis, rats were injected with 3H2O. Plasma H2O incorporation into BAT lipids was significantly greater in VMNL rats. Likewise, BAT lipid content was higher in obese rats. In another experiment BAT was incubated with U-14C-glucose to evaluate glucose utilization by BAT. 14C-glucose was oxidized and incorporated into both lipids and glycogen more rapidly by obese than by normal rat BAT. Glycogen content was greater in VMNL rats. Tissues were also incubated with 1-14C-pyruvate and 2-14C pyruvate. Pyruvate incorporation into glyceride glycerol and oxidation of 2-14C pyruvate through the Krebs cycle were similar in both obese and control rats. However, the incorporation of pyruvate into glyceride fatty acids was increased in VMNL rats. The results indicate that both fatty acid and lipid synthesis are increased in BAT of obese rats whereas lactate production is decreased and Krebs cycle activity is normal. Some of these changes appear to be independent of the level of food intake.     

Dopaminergic suppression of angiotensin II-induced aldosterone secretion in man: differential responses during sodium loading and depletion

Previous studies have shown that aldosterone secretion may be inhibited by dopaminergic mechanisms in man. Dopamine does not inhibit aldosterone responses to angiotensin II in sodium-replete normal subjects. Since sodium deficiency is associated with a reduction in renal dopamine formation, we investigated the effect of dopamine on angiotensin II-induced aldosterone secretion in the sodium-depleted state. Six normal subjects in balance at 10 mEq sodium intake (UNaV 17 +/- 2 meq/24 hr) received dopamine 4 micrograms/kg/min or vehicle for 210 minutes on two consecutive days. After 60 minutes of the dopamine or vehicle infusion, the subjects received successive 30-minute infusions of angiotensin II in increasing doses of 0.5, 1, 2, 4 and 6 picomol/kg/min. Control plasma aldosterone concentrations before vehicle or dopamine were 15 +/- 3 (mean 1 +/- SE) and 25 +/- 3 ng/dL, respectively. Aldosterone responses to angiotensin II were greater with vehicle than dopamine at angiotensin II doses of 4 and 6 picomol/kg/min (P less than 0.025). The slope of angiotensin-aldosterone dose-response curve was steeper with vehicle (0.33) than with dopamine (0.16), P less than 0.01. Serum prolactin concentrations were lower with dopamine (1.6 +/- 0.8 ng/mL) than with vehicle (6.4 +/- 1.2 ng/mL, P less than 0.05) by 120 minutes of infusion and remained suppressed with dopamine for the remainder of the dopamine infusion. Diastolic blood pressure was higher (P less than 0.05) with vehicle than with dopamine at angiotensin II doses of 2, 4, and 6 picomol/kg/min. Dopamine administration was associated with an increase in plasma cortisol concentration from 90 to 150 minutes of infusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)