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Biomedical subjects

T L Goodfriend

Publications and source records attributed to T L Goodfriend.

At least 37 records · Page 2Linked to original sources
PubMed1996

Fatty acids enhance neurovascular reflex responses by effects on alpha 1-adrenoceptors.

Abnormalities in plasma nonesterified fatty acids (NEFAs) may contribute to increased vascular alpha-adrenergic tone in obese hypertensive patients, because raising NEFAs locally enhances vascular reactivity to exogenously infused phenylephrine. However, responses to exogenous phenylephrine, a relatively selective alpha 1-adrenoceptor agonist, may not reflect the physiologically more important response to endogenous norepinephrine, a nonselective alpha-adrenoceptor agonist. To study the effects of NEFAs on vascular responses to endogenously released norepinephrine, dorsal hand venoconstrictor responses to thigh cuff inflation were quantified in nine healthy volunteers during coinfusion of Intralipid with heparin to raise fatty acids locally. Intralipid-heparin, which approximately doubled local linoleic and oleic acid concentrations (P < 0.05), increased the magnitude and duration of the venoconstrictor response to thigh cuff inflation (P < 0.005) and also enhanced venoconstrictor responses to locally infused phenylephrine but not clonidine, a relatively selective partial alpha 2-adrenoceptor agonist. The results of this study indicate that NEFAs enhance reflex vasoconstrictor responses largely through local effects on the vascular alpha 1-adrenoceptor and raise the possibility that fatty acids contribute to increased neurovascular tone in obese hypertensive patients.

Adrenergic alpha-Agonists↗
PubMed1996

Obesity hypertension is related more to insulin's fatty acid than glucose action.

Although resistance to insulin-mediated glucose disposal has emerged as a link between abdominal obesity and hypertension, abnormalities of nonesterified fatty acid metabolism may play a greater role. Analyses were performed on existing data from 17 abdominally obese subjects (11 hypertensive, 6 normotensive) to determine whether fatty acid concentration and turnover were related to blood pressure independently of hyperinsulinemia and resistance to insulin-mediated glucose disposal. Glucose utilization, fatty acid concentration, and fatty acid turnover were obtained fasting and during euglycemic hyperinsulinemia at 10 and 40 mU/m/min. Analyses were also performed on another group of 30 subjects with a wide range of risk factors who had blood pressure data as well as glucose and fatty acid measurements during an insulin tolerance test. Fatty acid concentration and turnover were markedly more resistant to suppression by insulin in obese hypertensive than in lean or obese normotensive individuals. In the 17 obese subjects, blood pressure measured at screening, in the laboratory, and over a period of 24 hours correlated significantly with fatty acid concentration and turnover but not with glucose disposal measured during the hyperinsulinemic clamp. These correlations remained significant after fasting insulin, the insulin area under the curve during an oral glucose tolerance test, and glucose disposal during the clamp were controlled for. In the second group of subjects, plasma fatty acids 15 minutes after intravenous insulin also correlated with blood pressure. These correlations remained significant after insulin and an index of sensitivity to insulin-mediated glucose disposal were statistically controlled for. The data indicate that blood pressure is related to the effects of insulin on fatty acid metabolism. The findings raise the possibility that resistance of hormone-sensitive lipase to insulin participates in elevating the blood pressure of abdominally obese hypertensive subjects by increasing fatty acid concentration and turnover.

Adult↗
PubMed1995

Relationships among plasma aldosterone, high-density lipoprotein cholesterol, and insulin in humans.

To investigate the pathogenesis of hypertension in patients with obesity and insulin resistance and to explore the role of plasma lipids, we studied 30 subjects at the end of 7 days of low (20 mEq/d) then high (200 mEq/d) sodium diets. Glucose and insulin tolerance tests were performed at the end of each week and blood and urine collected for measurements of plasma aldosterone, renin activity, electrolytes, insulin, and lipoproteins. There was a strong negative correlation between plasma aldosterone and high-density lipoprotein cholesterol during both diets. There were weaker positive correlations between plasma aldosterone and insulin or triglycerides. When the aldosterone-renin ratio was the dependent variable and the correlation controlled for serum potassium, the inverse relationship with high-density lipoprotein cholesterol and the positive correlation with insulin remained, but only during the high salt diet. Subjects were divided into three groups based on high-density lipoprotein cholesterol. Subjects with the lowest high-density lipoprotein cholesterol levels showed the highest aldosterone, plasma triglycerides, body mass index, and waist-to-hip ratio. Those subjects also demonstrated the greatest resistance to insulin action on glucose and plasma unesterified fatty acids. There was a weak direct correlation between plasma aldosterone and systolic blood pressure during the high salt diet. These data suggest that high aldosterone levels may be a link between dyslipidemia, insulin resistance, and hypertension, a relationship made more evident by high salt intake.

Adult↗
PubMed1995

Fatty acids enhance vascular alpha-adrenergic sensitivity.

Hypertensive patients are heavier and have a more centralized body fat distribution, which is associated with risk factor clustering and resistance to insulin's actions, including suppression of plasma nonesterified fatty acids. We postulated that abnormalities of nonesterified fatty acids contribute to the increased vascular alpha-adrenergic reactivity and tone observed in our previous studies of obese hypertensive subjects. To test this hypothesis, in two separate protocols 10% Intralipid was infused into a dorsal hand vein with heparin to activate lipoprotein lipase and raise fatty acid levels locally. In protocol 1, the effects of Intralipid/heparin compared with those of 5% dextrose/heparin on dorsal hand vein sensitivity to phenylephrine were assessed by use of the linear variable differential transformer technique in 8 normotensive subjects. In protocol 2, the effects of Intralipid/heparin were compared with those of saline/heparin on hand vein responses to both phenylephrine and angiotensin II in 11 normotensive African American women. Intralipid/heparin reduced the dose of phenylephrine required to produce 50% of the maximal venoconstrictor response from 582 to 137 ng/min (compared with dextrose/heparin, P < .01) in protocol 1 and from 293 to 137 ng/min (compared with saline/heparin, P < .01) in protocol 2. Intralipid/heparin did not significantly alter hand vein responses to angiotensin compared with saline/heparin. These data suggest that abnormalities of nonesterified fatty acids in obese hypertensive patients with risk factor clustering may contribute to their increased neurovascular tone.

Adrenergic alpha-Agonists↗
PubMed1995

Lead increases aldosterone production by rat adrenal cells.

Exposure to lead has been postulated to contribute to elevated blood pressure in humans and has been shown to raise blood pressure in animals. The mechanism of action of lead on blood pressure is unknown. We fed lead to rats in their drinking water and then examined the production of aldosterone by their adrenal cells in vitro. We also measured excretion of aldosterone and corticosterone by intact rats stimulated with corticotropin, with and without lead treatment. At a dose (273 ppm) that raised blood levels to 30 to 40 micrograms/dL, comparable to blood levels in exposed humans, lead induced increased aldosterone secretion in vitro and in vivo. The effect of lead was most evident when cells or animals were stimulated with aldosterone secretagogues. Experiments in vitro indicate that exposure to lead in vivo increases activity of one or more steps in the late pathway of aldosterone biosynthesis. The results suggest that the hypertensive effect of lead involves relative hyperaldosteronism and may be most evident when secretion of this hormone is stimulated.

Adrenal Glands↗
PubMed1995

Oleic acid inhibits endothelial nitric oxide synthase by a protein kinase C-independent mechanism.

Many obese hypertensive individuals have a cluster of cardiovascular risk factors. This cluster includes plasma nonesterified fatty acid concentrations and turnover rates that are higher and more resistant to suppression by insulin than in lean and obese normotensive individuals. The higher fatty acids may contribute to cardiovascular risk in these patients by inhibiting endothelial cell nitric oxide synthase activity. To test this hypothesis, we quantified the effects of oleic (18:1[cis]) and other 18-carbon fatty acids on nitric oxide synthase activity in cultured bovine pulmonary artery endothelial cells by measuring the conversion of [3H]L-arginine to [3H]L-citrulline. Oleic acid (from 10 to 100 mumol/L) caused a concentration-dependent decrease in nitric oxide synthase activity at baseline and during ATP and ionomycin (Ca2+ ionophore) stimulation. At 100 mumol/L, linoleic (18:2[cis]) and oleic acids caused similar reductions of nitric oxide synthase activity, whereas elaidic (18:1[trans]) and stearic (18:0) acids had no effect. Oleic acid also inhibited the endothelium-dependent vasodilator response to acetylcholine in rabbit femoral artery rings preconstricted with phenylephrine (P < .05) but had no effect on the response to nitroprusside. The pattern of 18-carbon fatty acid effects on nitric oxide synthase activity in endothelial cells is consistent with activation of protein kinase C. Although oleic acid increased protein kinase C activity in endothelial cells, neither depletion of protein kinase C by 24-hour pretreatment with phorbol 12-myristate 13-acetate nor its inhibition with staurosporine eliminated the inhibitory effect of oleic acid on nitric oxide synthase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Renin and aldosterone are higher and the hyperinsulinemic effect of salt restriction greater in subjects with risk factors clustering.

Separate lines of evidence suggest that abdominal obesity, insulin, and renin are independent risk factors for coronary heart disease. Since insulin levels are higher in abdominally obese subjects and may enhance renin and aldosterone production, these risk factors may not be entirely independent. Moreover, the renin-angiotensin system may contribute to insulin resistance. These observations suggest that some inconsistencies in the literature regarding the effects of salt restriction on insulin may be explained by baseline anthropometric and metabolic differences in the subjects studied. To examine these issues, 29 volunteers with a range of risk factors were studied after 1 week each on isocaloric 20 and 200 mmol/day NaCl diets. Measurements included ambulatory blood pressures, plasma renin and aldosterone, and responses to oral glucose and intravenous insulin. Subjects were divided into three groups based on a composite score reflecting the risk factor cluster associated with abdominal obesity and hyperinsulinemia. The nine subjects with the highest scores had significantly greater values for renin and aldosterone on both the high and low salt diets than the nine subjects with the lowest scores. Fasting insulin and triglycerides, the insulin response to oral glucose, and plasma aldosterone all rose significantly more with salt restriction in the high than in the low risk subjects. Plasma renin activity also tended to increase more on the low salt diet in the high risk group. Ambulatory blood pressures were greater on the low than the high salt diet only in the high risk group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Assessment of blood pressure during treatment with naproxen or ibuprofen in hypertensive patients treated with hydrochlorothiazide.

This study determined the effect of nonsteroidal anti-inflammatory drug (NSAID) administration on blood pressure in hypertensive patients taking hydrochlorothiazide (HCTZ). Ninety-seven patients with mild essential hypertension and a musculoskeletal indication for NSAID use were studied in a three-phase, multi-center, double-blind, randomized, parallel study based in 15 academic and community clinics. Patients served as their own controls. Patients with stable hypertension, not taking antihypertensive or NSAID medications, were treated with HCTZ 50 mg/day. After 4 to 5 weeks of treatment and documented stable blood pressure, naproxen 375 mg twice a day or ibuprofen 800 mg three times a day was added. Blood pressure was measured at 2 and 4 weeks of NSAID therapy. The average diastolic blood pressure was 97.5 +/- 2.4 mm Hg and the average of the mean arterial pressure (MAP) was 116.8 +/- 6.04 before treatment with HCTZ. Hydrochlorothiazide treatment decreased diastolic blood pressure to 83.1 +/- 5.6 mm Hg, and MAP to 101.1 +/- 6.5 mm Hg. With naproxen or ibuprofen treatments, mean diastolic blood pressure increased less than 3 mm Hg. At 2 weeks, ibuprofen increased diastolic blood pressure by 2.6 mm Hg (P = .004) and naproxen increased diastolic blood pressure 0.7 mm Hg (P = .40). Both ibuprofen and naproxen significantly increased diastolic pressure at 4 weeks (2.1 mm Hg, P = .042; and 1.8 mm Hg, P = .043, respectively). There was no correlation between the pre-NSAID blood pressure and the magnitude of change after 2 or 4 weeks of treatment. Changes in MAP reflected a pattern similar to diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Fatty acids may regulate aldosterone secretion and mediate some of insulin's effects on blood pressure.

Experiments in vitro and observation made in humans suggest that some unesterified fatty acids (FA) participate, as inhibitors, in the regulation of aldosterone secretion. Removal of FA from adrenal glomerulosa cells with albumin increases the responses to angiotensin II (AII) and dibutyryl cyclic AMP. Micromolar concentrations of some FA including arachidonic, oleic, linoleic, eicosapentaenoic, and docosahexaenoic inhibit aldosterone secretion by adrenal glomerulosa cells. Inhibition is specific--some acids like stearic are inactive, and the adrenal fasciculata is relatively resistant to inhibition. Oleic acid rapidly and reversibly inhibits aldosterone secretion by perfused dog adrenals. Observations in vivo suggest a reciprocal relationship between plasma levels of FA and aldosterone: insulin infusion into dogs lowers plasma FA and increases adrenal responsiveness to All; salt infusions into humans increase plasma FA as aldosterone falls; plasma FA are low in low-renin essential hypertension where adrenal responsiveness to All is high; plasma FA are inversely correlated with ratios of aldosterone to renin in black hypertensives; and plasma FA are high in some seriously ill patients whose aldosterone levels are inexplicably low. All receptors and the final step of aldosterone biosynthesis, oxidation at the 18 position, are the adrenal sites most sensitive to FA. Insulin's antinatriuresis may be mediated in part by its ability to lower plasma FA and thereby enhance adrenal response to secretagogues.

Aldosterone↗
PubMed1993

Lateral diffusion and fatty acid composition in vascular smooth muscle membrane from stroke-prone spontaneously hypertensive rats.

We measured membrane fluidity and fatty acid composition in cultured vascular smooth muscle cells from stroke-prone spontaneously hypertensive and Wistar-Kyoto normotensive rats. Membrane fluidity was measured as a lateral diffusion of 5 N (octadecanoyl) aminofluorescein using fluorescence microscopy and fluorescence recovery after photobleaching. Fatty acid composition of membrane fractions was measured using high performance liquid chromatography. Lateral diffusion was significantly lower (the membrane had lower fluidity) in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats as compared to those cells isolated from Wistar-Kyoto reference strain. The ratio of arachidonic acid to total fatty acids was 0.058 +/- 0.007 in the plasma membrane from stroke-prone spontaneously hypertensive rats and 0.036 +/- 0.005 in that from Wistar-Kyoto rats, P = .005. Similarly, the ratios of arachidonic to oleic acid and arachidonic to palmitic acid were significantly greater in cells from stroke-prone spontaneously hypertensive rats (P = .002 for difference in each ratio). These results show decreased lateral diffusion (decreased membrane fluidity) in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats. This is associated with increased content of arachidonic acid, the major precursor of prostaglandins and other eicosanoids. We postulate that local changes in the unsaturated fatty acid composition related to arachidonic acid storage and release contribute to reduced membrane fluidity in stroke-prone spontaneously hypertensive rats.

Animals↗
PubMed1993

Mechanism of fatty acid inhibition of aldosterone synthesis by bovine adrenal glomerulosa cells.

Previous work from this laboratory has suggested that the adrenal glomerulosa is under tonic inhibition by fatty acids. The purpose of the present work was to define the mechanism by which fatty acids inhibit aldosterone synthesis. Experiments with isolated bovine adrenocortical cells showed the following. 1) Fatty acids inhibited angiotensin-II-stimulated and (Bu)2cAMP-stimulated aldosterone synthesis with similar potencies. 2) Inhibition of aldosterone synthesis was highly dependent on fatty acid chain length and degree of unsaturation as well as on configuration of double bonds. Oleic acid was the most potent inhibitor among fatty acids prominent in plasma. 3) Cortisol synthesis was less sensitive to oleic acid inhibition than was aldosterone synthesis. 4) Pregnenolone synthesis by angiotensin-II-stimulated adrenal glomerulosa cells was relatively insensitive to oleic acid. 5) For both glomerulosa and fasciculata cells, cortisol synthesis from 21-deoxycortisol, which requires the participation of P450(21), was relatively insensitive to fatty acids. Cortisol synthesis from corticosterone by fasciculata cells, which requires the participation of P450(17) alpha, was also insensitive to oleic acid. These are microsomal enzymes. 6) In glomerulosa cells, aldosterone synthesis from added corticosterone, which requires the 18-oxidase function of P450(11) beta, a mitochondrial enzyme, was potently inhibited by fatty acids; cortisol synthesis from 11-deoxycortisol by glomerulosa cells, which requires P450(11) beta, was less sensitive to inhibition, and cortisol synthesis from 11-deoxycortisol by fasciculata cells was even less sensitive. 7) Aldosterone synthesis from exogenous 18-hydroxycorticosterone was potently inhibited by oleic acid. Thus, fatty acids are potent inhibitors of the 18-oxidase function of the mitochondrial enzyme P450(11) beta, whereas nonmitochondrial steroidogenic enzymes and the 11-hydroxylase function of P450(11) beta are relatively insensitive to fatty acids. The special sensitivity of aldosterone synthesis to fatty acid inhibition appears to result from the unusual susceptibility of the 18-oxidase function of the mitochondrial steroidogenic enzyme P450(11) beta. This mechanism would allow differential regulation of aldosterone vs. cortisol production by unesterified fatty acids.

Albumins↗
PubMed1993

Bovine adrenal glomerulosa and fasciculata cells exhibit 28.5-kilodalton proteins sensitive to angiotensin, other agonists, and atrial natriuretic peptide.

Protein synthesis by bovine adrenal glomerulosa and fasciculata cells in response to various modulators of steroid synthesis was examined using [35S]methionine labeling and two-dimensional gel electrophoresis. Both cell types responded to steroidogenic stimuli with rapid changes in a family of 28- to 30-kilodalton (kDa) proteins similar to those described in rat fasciculata by Epstein and Orme-Johnson. In glomerulosa, angiotensin-II (AII), potassium, and (Bu)2cAMP stimulated the appearance of two 28.5-kDa proteins (no. 3 and 4) with pI values of 6.44 and 6.33 and decreased labeling of two other 28.5-kDa proteins (no. 1 and 2) with pI values of 6.9 and 6.59. The rank order of potency on aldosterone synthesis and that on proteins 1-4 were the same: (Bu)2cAMP > AII > potassium. Atrial natriuretic peptide blocked the effects of AII on all four proteins and on aldosterone synthesis. Adrenal secretagogues also affected labeling of four slightly larger (30 kDa) proteins (no. 5-8). Corresponding proteins in each quartet are separated by the same difference in isoelectric points. These eight proteins may represent a core protein systematically modified in a number of ways. Aldosterone synthesis in glomerulosa, like glucocorticoid synthesis in fasciculata, requires ongoing protein synthesis. The 28- to 30-kDa proteins increased by steroidogenic stimuli in both cells and decreased by atrial natriuretic peptide in glomerulosa may be the proteins whose synthesis is crucial to acute control of steroidogenesis. Our results indicate that these proteins are made in response to calcium- or calcium/phosphoinositide-dependent mechanisms as well as by cAMP.

Angiotensin II↗
PubMed1992

Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men.

There is a widespread interest in fish oil as a dietary supplement and possible nonpharmacologic adjunct in the treatment of hypertension. The effect of dietary fish oil on blood pressure is controversial and the effect on systemic hemodynamics and regional vascular reactivity in humans is unknown. To address these questions, a double-blind, placebo-controlled, crossover study on the effect of dietary fish oil substitution was performed during a carefully controlled diet in 8 normotensive men. Systemic hemodynamics and the forearm vascular response to intrabrachial artery infusions of norepinephrine, phentolamine and angiotensin II were obtained. Compared with a safflower oil placebo, dietary fish oil had no effect on cardiac output (6.42 +/- 0.38 vs 6.87 +/- 0.28 liters/min, p = not significant) or 24-hour blood pressure (122/68 +/- 3/3 vs 122/68 +/- 3/2 mm Hg, p = not significant). The vascular response to norepinephrine and phentolamine was unchanged. Fish oil, however, significantly (p < 0.05) reduced forearm vascular resistance responses to angiotensin II. These changes were associated with a reduction in plasma triglycerides (64 +/- 9 vs 39 +/- 4 mg/dl, p = 0.02) and an increase in plasma eicosapentaenoic acid levels (0.51 +/- 0.25 vs 1.72 +/- 0.35 microM, p < 0.05). Substitution of a moderate dose of fish oil for fat in a "Western diet" selectively attenuates the vascular response to angiotensin independently of changes in alpha-adrenergic vasoconstriction or systemic hemodynamics.

Adult↗
PubMed1991

Sphingosine inhibits angiotensin-stimulated aldosterone synthesis.

Sphingosine and other protein kinase C inhibitors were tested for their ability to inhibit aldosterone synthesis by bovine adrenal glomerulosa cells. Sphingosine inhibited angiotensin (AII)-stimulated aldosterone synthesis (IC50 of 5 microM). At doses that totally blocked steroidogenesis, sphingosine did not affect protein synthesis or [125I]AII binding to cells. Sphingosine also inhibited dibutyryl cyclic AMP (dbcAMP)-stimulated aldosterone synthesis. Sphingosine inhibited pregnenolone synthesis from cholesterol, but not the conversion of progesterone or 20 alpha-hydroxycholesterol to aldosterone. These results suggest that sphingosine inhibits steroidogenesis at a locus close to that where stimulation occurs by AII and dbcAMP. Other protein kinase C inhibitors were tested. Retinal, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), and staurosporine inhibited aldosterone synthesis stimulated by AII and dbcAMP. Retinal and H-7 also inhibited progesterone conversion to aldosterone, and retinal blocked [125I]AII binding. Staurosporine was more specific, inhibiting AII-stimulated aldosteronogenesis at concentrations which had little effect on conversion of progesterone to aldosterone. Because they inhibited dbcAMP stimulation, none of the inhibitors was sufficiently specific to use as a probe of the role of protein kinase C. The IC50 of sphingosine suggests that this or related products of lipid hydrolysis could act as endogenous regulators of adrenal cell function.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Salt loads raise plasma fatty acids and lower insulin.

Some fatty acids are potent inhibitors of angiotensin binding and aldosterone production in adrenal glomerulosa cells and thereby may be involved in regulating salt and water balance. To study the possible regulation of fatty acids by salt, we measured the levels of unesterified fatty acids in plasma from patients subjected to extremes of dietary salt intake and saline infusion. Insulin and catecholamines, two known regulators of plasma fatty acids, also were measured. Infusion of 2 l saline over 4 hours caused the levels of most unesterified fatty acids to rise. Total unesterified fatty acids rose 60-100%. A high salt diet caused a smaller rise in total unesterified fatty acids (approximately 33%). In both instances, oleic and palmitoleic acids showed the greatest proportionate increases, whereas stearic acid was relatively unaffected. When salt loads were administered by either intravenous or dietary routes, plasma insulin levels fell by approximately 50%. Plasma norepinephrine increased after saline infusion but not during a high salt diet. Postsaline levels of fatty acids correlated inversely with postsaline levels of aldosterone, supporting a possible role for fatty acids as physiological regulators of the adrenal glomerulosa. A rise in plasma fatty acids and fall in insulin in response to salt loads could act in concert to increase sodium excretion, constituting a physiological mechanism contributing to salt and water balance.

Chromatography, High Pressure Liquid↗
PubMed1991

Fatty acids are potential endogenous regulators of aldosterone secretion.

Adrenal glomerulosa cells washed with delipidated albumin produced increased amounts of aldosterone in response to angiotensin-II (AII) or (Bu)2cAMP. Albumin treatment also increased binding of 125I-labeled AII to high affinity binding sites on adrenal cells. Lipid extracts of albumin solutions that were used to wash cells inhibited AII binding and aldosterone responses by washed glomerulosa cells. Chromatographic fractionation and mass spectroscopic analysis indicated that the inhibitors removed from cells by albumin were long chain fatty acids. Exogenous fatty acids not only inhibited AII binding, but they inhibited basal aldosterone production and increments in aldosterone caused by AII or dbcAMP, suggesting an effect on postreceptor steps in aldosteronogenesis. The most potent and most abundant fatty acids removed from adrenal cells were oleic, linoleic, and arachidonic. These fatty acids inhibited at micromolar concentrations in the absence of albumin and at somewhat higher concentrations in its presence. Cells that had been washed, then inhibited by exogenous oleic acid in vitro, were restored to their enhanced responsiveness by a second albumin wash, making it unlikely that cell damage is the mechanism of inhibition by fatty acids. Responses of fasciculata cells were not potentiated by albumin washes, and cortisol production was less sensitive than aldosterone production to exogenous fatty acids. Binding of ANP to glomerulosa cells was not affected by albumin or fatty acids. These results combined with clinical correlations make it plausible that unesterified fatty acids are naturally occurring regulators of the adrenal glomerulosa. Insulin's ability to lower plasma levels of fatty acids may be one way that it causes sodium retention.

Aldosterone↗