Oxytocin response to controlled dietary sodium and angiotensin II among healthy individuals.

Oxytocin, while classically known for its role in parturition, lactation, and social behavior, also has been implicated in the control of sodium homeostasis in animal models. To improve our understanding of oxytocin physiology in humans, we measured basal oxytocin levels under low- and liberal-dietary-sodium conditions and following a peripheral angiotensin II (ANG II) infusion. Ten healthy individuals underwent a 6-day standardized low-sodium diet and a 6-day liberal-sodium diet. Each diet was followed by a graded ANG II infusion for 30-min sequential intervals at doses of 0.3, 1.0, and 3.0 ng·kg-1·min-1. Fasting serum oxytocin was assessed before and after ANG II infusion. Basal oxytocin levels (1,498.5 ± 94.7 vs. 1,663.3 ± 213.9 pg/ml, P = 0.51) did not differ after the low- and liberal-sodium diets. Following the ANG II infusion, ANG II levels and mean arterial pressure significantly increased as expected. In contrast, the ANG II infusion significantly lowered oxytocin levels from 1,498.5 ± 94.7 vs. 1,151.7 ± 118.1 pg/ml ( P < 0.001) on the low-sodium diet and from 1,663.3 ± 213.9 vs. 1,095.2 ± 87.4 pg/ml ( P = 0.03) on the liberal-sodium diet. The percent change in oxytocin following the ANG II infusion did not differ by sodium diet (-25 ± 5% vs. -28 ± 7% low- vs. liberal-sodium conditions, P > 0.99). Dietary sodium intake did not affect circulating oxytocin levels among healthy individuals. Systemic oxytocin levels were significantly suppressed following a peripheral ANG II infusion independent of dietary sodium conditions.

Significant Association of Aldosterone and Liver Fat Among HIV-Infected Individuals With Metabolic Dysregulation.

OBJECTIVE: Fatty liver disease is increased among individuals with HIV. We sought to explore how aldosterone, a key hormone linked to insulin resistance and inflammation, relates to liver fat in the large population of individuals with HIV and metabolic abnormalities. METHODS: Forty-six individuals with HIV and increased waist circumference and dysglycemia were assessed for liver fat using proton magnetic resonance spectroscopy. Serum aldosterone level was obtained following strictly controlled posture conditions and a standardized sodium diet and was related to liver fat. RESULTS: Among the entire group [median (interquartile range) liver fat: 5% (3%, 12%) and homeostatic model assessment of insulin resistance: 1.74 (1.21, 2.83)], serum aldosterone significantly correlated with liver fat (r = 0.31; P = 0.049). Liver fat level was significantly higher in those with aldosterone above vs below the median [8% (3%, 20%) vs 4% (2%, 10%); P = 0.02]. In the presence of metabolic syndrome, individuals with aldosterone levels above vs below the median had markedly elevated liver fat values [14% (9%, 23%) vs 5% (3%, 12%); P = 0.005] and increased presence of fatty liver disease (FLD; 92% vs 50%; P = 0.02). Controlling for metabolic syndrome, hepatitis C virus, and alcohol use, aldosterone was a significant and independent predictor of liver fat (ß estimate: 0.6038, P = 0.01; overall model r 2 = 0.41, P = 0.0005) and FLD (OR: 1.38, P = 0.02; overall model r 2 = 0.28, P = 0.002). CONCLUSION: These data highlight a robust association between aldosterone and liver fat among individuals with HIV and metabolic dysregulation. Increased aldosterone may be a risk factor for liver fat accumulation among the population with HIV.

Epicardial adipose tissue volume and cardiovascular risk indices among asymptomatic women with and without HIV.

BACKGROUND: Mechanisms underlying the heightened myocardial infarction risk among HIV-infected women (versus non-HIV-infected women) remain unclear. Our objectives were to assess epicardial adipose tissue (EAT) volume and its associations among asymptomatic women with and without HIV. METHODS: A total of 55 HIV-infected and 27 non-HIV-infected women without known cardiovascular disease who underwent cardiac CT and metabolic/immune phenotyping were included. EAT volume derived from CT was compared among women with and without HIV, and within-group EAT associations were assessed. Next, immune and atherosclerotic plaque parameters were compared among groups stratified by HIV serostatus and high/low EAT (defined in reference to median EAT for each serostatus group). RESULTS: Asymptomatic HIV-infected women and age-matched non-HIV-infected women with comparable mean body mass index (28 ±1 versus 29 ±1 kg/m2) had similar median (IQR) volumes of EAT (54 [41-79] versus 65 [41-78] cm3; P>0.05); however, different within-group associations were noted. Markers of monocyte activation/arterial inflammation differed by HIV serostatus/EAT volume subgroup (CXCL10 [P=0.02], sCD163 [P=0.004], sCD14 [P=0.03], Lp-PLA2 [P=0.04]; P for overall ANOVA) and were highest among HIV-infected women with excess EAT (versus HIV-infected women without excess EAT, non-HIV-infected women with excess EAT and non-HIV-infected women without excess EAT). The percentage of segments with non-calcified coronary plaque also differed by HIV serostatus/EAT volume subgroup and was highest among HIV-infected women with excess EAT. CONCLUSIONS: Asymptomatic women with and without HIV have similar volumes of EAT, but drivers of EAT may differ between groups. HIV-infected women with excess EAT have highest-level immune activation and the highest percentage of non-calcified plaque. Future studies are needed to determine whether EAT contributes pathogenetically to HIV-associated cardiovascular disease in women.

Randomized, Placebo-Controlled Trial to Evaluate Effects of Eplerenone on Metabolic and Inflammatory Indices in HIV.

Context: HIV-infected individuals demonstrate increased renin-angiotensin-aldosterone system activation in association with visceral adiposity, insulin resistance, and inflammation. A physiologically based treatment approach targeting mineralocorticoid receptor (MR) blockade may improve metabolic and inflammatory indices in HIV. Objective: To investigate effects of eplerenone on insulin sensitivity, inflammatory indices, and other metabolic parameters in HIV. Design: Six-month, double-blind, randomized, placebo-controlled trial. Setting: Academic clinical research center. Participants: HIV-infected individuals with increased waist circumference and abnormal glucose homeostasis. Intervention: Eplerenone 50 mg or placebo daily. Outcome: The primary end point was change in insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp technique. Secondary end points included change in body composition and inflammatory markers. Results: Forty-six individuals were randomized to eplerenone (n = 25) vs placebo (n = 21). Eplerenone did not improve insulin sensitivity [0.48 (-1.28 to 1.48) vs 0.43 (-1.95 to 2.55) mg/min/µIU/mL insulin; P = 0.71, eplerenone vs placebo] when measured by the gold standard euglycemic-hyperinsulinemic clamp technique. Intramyocellular lipids (P = 0.04), monocyte chemoattractant protein-1 (P = 0.04), and high-density lipoprotein (P = 0.04) improved among those randomized to eplerenone vs placebo. Trends toward decreases in interleukin-6 (P = 0.10) and high-sensitivity C-reactive protein (P = 0.10) were also seen with eplerenone vs placebo. Plasma renin activity and aldosterone levels increased in the eplerenone vs placebo-treated group, demonstrating expected physiology. MR antagonism with eplerenone was well tolerated among the HIV population, with no considerable changes in blood pressure or potassium. Conclusion: MR blockade may improve selected metabolic and inflammatory indices in HIV-infected individuals. Further studies are necessary to understand the clinical potential of MR antagonism in HIV.

Acute hyperinsulinemia effects on systemic markers of immune activation in HIV.

: The well treated HIV population remains at risk for insulin resistance and chronic immune activation. We tested the effects of acute hyperinsulinemia on inflammation in HIV. Twenty HIV-infected and 10 non-HIV-infected individuals well matched for BMI underwent oral glucose tolerance testing to stimulate insulin secretion and assess for changes in circulating soluble CD163, soluble CD14, and monocyte chemoattract protein 1. Soluble CD14 decreased significantly after stimulation of hyperinsulinemia and no significant changes in soluble CD163 or monocyte chemoattract protein 1 were demonstrated in HIV-infected and non-HIV-infected groups.

Optic neuropathy following an altitude exposure.

This case report describes a 20-yr-old man who presented with retro-orbital pain and blurred vision in his left eye 3 wk after an altitude exposure in a hypobaric chamber. He was found to have significant deficits in color vision and visual fields consistent with an optic neuropathy in his left eye. The patient was diagnosed with decompression sickness and treated with hyperbaric oxygen with a U.S. Navy Treatment Table VI. All signs and symptoms resolved with a single hyperbaric oxygen treatment but recurred. A head MRI revealed a left frontoethmoid sinus opacity. A concomitant sinusitis was diagnosed. The patient had full resolution of symptoms after a total of four hyperbaric oxygen treatments and antibiotic therapy at 6-wk follow-up. Although a para-infectious etiology for this patient's optic neuropathy cannot be excluded, his history of altitude exposure and significant, rapid response to hyperbaric oxygen treatment strongly implies decompression sickness in this case.