Background: Previous research on bipolar disorder demonstrates greater-than-expected vascular dysfunction later in the course of illness, proportionate to the cumulative burden of mood symptoms. However, little is known about the effect of acute mood states on vascular function. Here, we examine the relation between vascular function and mood state in individuals with bipolar disorder. Materials and Methods: This prospective study followed forty individuals with bipolar disorder for up to 6 months. The participants were assessed for mood state and vascular function at baseline, 2 weeks, and 6 months. Mood state was determined using the clinician-administered Montgomery–Šsberg Depression Rating Scale and Young Mania Rating Scale. Vascular function was assessed by flow-mediated dilation (FMD) of the brachial artery, forearm vascular resistance (FVR), and arterial stiffness. Results: The participants had a mean age of 30.1 years, and 75% were male. Primary outcome measures such as FMD and nitroglycerine-mediated dilation were not found to have statistically significant associations with depressive or manic symptoms. In unadjusted models, higher manic symptoms were significantly associated with increased FVR nitroprusside-mediated dilation and diastolic blood pressure. In adjusted models, higher depressive symptoms were significantly associated with increases in augmentation index adjusted for heart rate of 75 bpm, and higher manic symptoms remained associated with increases in diastolic blood pressure. Conclusion: FMD may have limited sensitivity as a biomarker for measuring short-term effects of mood state. Long-term prospective studies are needed to clarify the temporal relation between chronic mood symptoms and vascular function in bipolar disorder.

Purpose: To evaluate the comparative effectiveness of 3 regional corticosteroid injections for uveitic macular edema (ME): periocular triamcinolone acetonide (PTA), intravitreal triamcinolone acetonide (ITA), and the intravitreal dexamethasone implant (IDI). Design: Multicenter, randomized clinical trial. Participants: Patients with uveitic ME. Methods: Patients were randomized 1:1:1 to receive 1 of the 3 therapies. Patients with bilateral ME were assigned the same treatment for both eyes. Main Outcome Measures: The primary outcome was the proportion of baseline (PropBL) central subfield thickness (CST) at 8 weeks (CST at 8 weeks/CST at baseline) assessed with OCT by masked readers. Secondary outcomes included >= 20% improvement and resolution of ME, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) events over 24 weeks. Results: All treatment groups demonstrated improved CST during follow-up. At 8 weeks, each group had clinically meaningful reductions in CST relative to baseline (PropBL: 0.77, 0.61, and 0.54, respectively, which translates to reductions of 23%, 39%, and 46% for PTA, ITA, and IDI, respectively). Intravitreal triamcinolone acetonide (PropBL ITA/PropBL PTA, hazard ratio [HR], 0.79; 99.87% confidence interval [CI], 0.65-0.96) and IDI (PropBL IDI/PropBL PTA, HR, 0.69; 99.87% CI, 0.56-0.86) had larger reductions in CST than PTA (P < 0.0001). Intravitreal dexamethasone implant was noninferior to ITA at 8 weeks (PropBL IDI/PropBL ITA, HR, 0.88; 99.87% CI, 0.71-1.08). Both ITA and IDI treatments also were superior to PTA treatment in improving and resolving uveitic ME. All treatment groups demonstrated BCVA improvement throughout follow-up. Both ITA and IDI groups had improvements in BCVA that was 5 letters greater than in the PTA group at 8 weeks (P < 0.004). The risk of having IOP >= 24 mmHg was higher in the intravitreal treatment groups compared with the periocular group (HR, 1.83; 95% CI, 0.91-3.65 and HR, 2.52; 95% CI, 1.29-4.91 for ITA and IDI, respectively); however, there was no significant difference between the 2 intravitreal treatment groups. Conclusions: Intravitreal triamcinolone acetonide and the IDI were superior to PTA for treating uveitic ME with modest increases in the risk of IOP elevation. This risk did not differ significantly between intravitreal treatments. (C) 2018 by the American Academy of Ophthalmology

To prospectively measure flow mediated vasodilation (FMD) in a cohort of women with risk factors for preeclampsia and to identify poor obstetrical outcomes associated with changes in FMD.

BACKGROUND Sildenafil, a selective phosphodiesterase-type-5 (PDE-5) inhibitor, produces vasodilation that improves erectile dysfunction and pulmonary hypertension. Sildenafil could also cause baroreflex sympathetic activation that would enhance vascular tone and oppose direct vasodilation. We tested the hypothesis that sildenafil administration increases sympathetically mediated vascular tone in healthy middle-aged men. METHODS We randomized 9 healthy, middle-aged, male volunteers (mean age 45±2 years) in a double-blind, crossover fashion to receive a single oral dose of sildenafil 100mg or placebo on 2 separate study days. Hemodynamics and forearm blood flow responses were measured at baseline, at 30 and 45 minutes after study drug administration, and then during intra-arterial infusions of vasoactive drugs. After sildenafil and placebo administration, intrabrachial medications were infused to test forearm alpha receptor sensitivity (norepinephrine), cyclic-AMP-mediated vasodilation (isoproterenol), and sympathetically mediated vascular tone (phentolamine) (adenosine was a control vasodilator). Blood samples were taken before and 60 minutes after study drug administration and at the end of the intrabrachial infusions for measurement of plasma norepinephrine concentrations. RESULTS Forearm vascular responses to norepinephrine, isoproterenol, and adenosine were not different after placebo and sildenafil administration. Percentage reduction in forearm vascular resistance during phentolamine was significantly lower after sildenafil than placebo (-73% ± 3% vs -63% ± 3%; P = 0.0002). Sildenafil significantly increased plasma norepinephrine compared with placebo 60 minutes after study drug administration and at the end of the study session (P = 0.02). CONCLUSIONS Sildenafil increased sympathetically mediated vascular tone in middle-aged healthy men. Alpha-adrenergic-mediated vasoconstriction may offset vasodilation during PDE-5 inhibition and may explain the significant hypotension observed in patients taking alpha-blockers with sildenafil.

Background We hypothesized that measurement of body fat would predict cardiovascular risk factors. Methods In a prospectively recruited cohort of 30 middle‐aged obese subjects with metabolic syndrome (55±9 yr; 28% male; BMI 38±4; mean±SD) we assessed the association of risk factors with BMI, waist circumference and body fat content (by air displacement plethysmography, skin fold thickness, and Body Adiposity Index (hip/(height1.5))‐18)) using regression analysis. Results Waist (118±11 cm) and body fat (plethysmography: 48±7%; skin fold: 41±4%; BAI: 41±8%) were elevated. Waist circumference was a significant and strong predictor of fasting glucose (100±10 mg/dl; R=0.499; P=0.008) and HDL‐cholesterol (57±14 mg/dl; R=0.537; P=0.003). BMI significantly predicted hsCRP (5.4±6.4 mg/dl; R=0.387; P=0.04), and weakly predicted systolic BP (129±15 mmHg; R=0.339; P=0.08). Importantly, body fat content (whether by air displacement plethysmography, skin fold thickness or BAI) did NOT associate with cardiovascular risk factors. Conclusion In obese subjects with metabolic syndrome, measurement of body fat content does NOT associate with BP, lipids, glucose or inflammation. Waist circumference and BMI are better predictors of cardiovascular risk factors. Grant Funding Source : NHLBI

Background: DHEA stimulates endothelial nitric oxide (NO) production in vitro and its prolonged use in humans improves vascular function.It is believed that this effect is mediated by metabolism of DHEA to androgens and estrogens.We hypothesized that DHEA action is mediated by a rapid, receptor-dependent, endothelial NO production pathway.We tested this hypothesis by studying the acute effect of a single oral dose of DHEA on vascular function in postmenopausal diabetic women.Design and Methods: This was a double blind, randomized, placebo controlled, cross-over study.Nine postmenopausal women with type 2 diabetes and 5 age-and weight-matched controls received 50 mg of DHEA or placebo in a random order one week apart.We examined forearm resistance vessel responses to intra-arterial nitroprusside, acetylcholine and verapamil.Results: There was no difference in baseline characteristics and steroid hormone levels between the groups.Following administration of DHEA, steroid hormone concentrations increased in both diabetics and controls indicating adequate absorption and metabolism of DHEA.Prior to administration of arterial vasodilators, there was no difference in baseline forearm blood flow between diabetics and controls and within each group in response to DHEA versus placebo.There was also no difference in the vasodilator-induced increment in blood flow between diabetics and controls and within each group in response to DHEA versus placebo.Conclusions: In postmenopausal women with diabetes, DHEA did not have any acute effect on basal or vasodilator stimulated forearm blood flow, despite evidence of systemic absorption and adequate vascular responses to endothelium and non-endothelium dependent vasodilators.

The role of neurohumoral factors in the sodium retention of nephrotic syndrome is controversial. We report a case with abrupt onset of severe nephrotic-range proteinuria and hypoalbuminemia due to membranous glomerulonephritis that was associated with renal salt wasting and hypovolemia without edema. Further evaluation showed hypoaldosteronism, hyporeninemia, and primary autonomic failure principally affecting the sympathetic nervous system, determined by the Valsalva maneuver. Administration of exogenous mineralocorticoid and oral salt caused edema and accelerated hypertension. The severe hypoaldosteronism likely was due to use of the angiotensin-converting enzyme inhibitor lisinopril, and it improved after this drug treatment was discontinued. The nephrotic proteinuria resolved after treatment with cyclosporine and prednisone, but the primary autonomic failure with hyporeninemic hypoaldosteronism persisted. The case shows that intratubular factors activated by nephrotic proteinuria are not sufficient to produce sodium retention in the absence of aldosterone and an intact sympathetic nervous system.

Upon receipt of the National Institutes of Health Clinical and Translational Science Award, the University of Iowa's Institute for Clinical and Translational Science committed to develop an infrastructure for research professionals. Three goals were established: (1) identification of research professionals within the University of Iowa, (2) development of an educational series, including orientation and continuing education, and (3) development of a mentoring system. The purpose of this paper is to describe the process of development, initiation, and outcomes of a successful networking, educational, and mentoring system crafted for research professionals at the University of Iowa.

The journal consistently attracts the most important and highly innovative papers from the current research; our commitment to rapid publication ensures that these are published in the fastest time possible. In addition to primary papers from world-renowned experts, the Journal contains authoritative reviews that summarize and evaluate the most significant recent developments. Also included are special reports, original short papers containing innovative and time-sensitive information. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. ​ Official Journal of the: International Society of Hypertension European Society of Hypertension

To the Editor: The community of physiological investigators who evaluate vascular function in intact humans have used the reactive hyperemia stimulus to measure conduit artery endothelium-dependent vasodilation for more than a decade. One component of this measure varies among the different groups: the location of the cuff that provides the ischemia that generates reactive hyperemia. Although theoretical variations have been postulated,1 the …

Background— Use of upper-arm arterial occlusion to induce reactive hyperemia, and endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, induces greater conduit vessel dilatation than lower-arm occlusion. However, brachial artery ischemia after upper arm arterial occlusion may make this approach unreliable. We studied whether upper or lower arm occlusions differ in their ability to detect endothelial dysfunction in cigarette smokers, and its improvement with an antioxidant strategy. Methods and Results— Ten cigarette smokers with a >20 pack year history and 10 age- and gender-matched healthy controls participated in a 2-phase randomized controlled study of xanthine oxidase inhibition, using a 600-mg oral dose of allopurinol administered beforehand. Endothelium-dependent dilatation was assessed using ultrasound-Doppler after lower and upper arm occlusion. After lower arm occlusion, FMD was significantly impaired in smokers compared with controls (3.8±1.1% versus 8.7±2.2%; P =0.001). However, after upper arm occlusion, brachial artery dilatation in smokers was higher (11.8±2.7%; P <0.0001 versus lower arm) and did not differ from controls (9.4±2.9%; P =0.3). There was no difference in endothelium-independent dilatation to sublingual nitroglycerin between smokers and controls. Inhibition of xanthine oxidase with allopurinol improved lower arm FMD (3.8±1.1 to 10.1±1.9%; P <0.0001), but did not improve upper arm FMD (11.8±2.7 to 14.1±3.7%; P =0.4). Conclusions— Although upper arm occlusion induces robust brachial vasodilatation, it cannot detect endothelial dysfunction induced by smoking or its improvement by inhibition of xanthine oxidase. The increase in brachial artery diameter with upper arm occlusion may be confounded by ischemia of the artery. Conduit artery FMD after release of lower arm occlusion appears to be a more valid method for assessment of endothelial function in humans.

OBJECTIVES:Arterial dysfunction occurs in obesity and diabetes. However, there is uncertainty about the relative contribution of endothelial dysfunction, smooth muscle dysfunction, or adrenergic hyperresponsiveness.METHODS AND RESULTS:We examined forearm resistance vessel responses to intra-arterial vasoactive agents in matched subjects on no antihyperglycemic medications classified as (1) Type 2 diabetes, (2) impaired fasting glucose (IFG), (3) obese, and (4) nonobese. Responses to both acetylcholine and nitroprusside were impaired in obese, IFG, and diabetic subjects compared to nonobese. However, diabetic and IFG subjects had no further impairment than normoglycemic obese subjects. Gender-specific data revealed that obese, IFG, and diabetic males compared to nonobese males demonstrated impaired responses to nitroprusside. However, among females, obese, IFG, and diabetic subjects demonstrated impaired acetylcholine-mediated responses. Multivariate analyses revealed that gender and adiposity, but not glycemia, were strongly related to acetylcholine and nitroprusside responses. Vasoconstriction to norepinephrine was greater in subjects with diabetes and IFG compared to nondiabetic obese controls.CONCLUSIONS:Microvascular vasodilator function is impaired in obesity, with little further impairment in IFG and Type 2 diabetes. Females appear more sensitive to the deleterious effect of obesity on endothelium-mediated resistance vessel function, and males to smooth muscle-mediated function. There is a specific increase in adrenergic vasoconstrictor responses in IFG and Type 2 diabetes independent of obesity.

Background: Nitric oxide is an endothelium dependent dilator, which may protect against atherosclerosis. Several Studies have shown a decrease in nitric oxide activity with aging, however none have assessed aging and atherosclerosis separately. We tested the hypothesis that aging blunts both basal and receptor-mediated endothelial nitric oxide release in humans.Methods: We examined whether forearm blood flow responses to intra-arterial acetylcholine, and nitroprusside, were altered with aging with and without co-infusion of an inhibitor of nitric oxide synthase (N-G-mono-methyl-L-arginine) in three groups Of human subjects a group with clinical atherosclerotic vascular disease (n = 31, 21 M), otherwise healthy elderly (n = 17, 13 M), and healthy young Controls (n = 15 8 M).Results: There was no difference in basal flows between the three groups. There was also no difference in the dilatation to either acetylcholine or nitroprusside responses between the AVD and the healthy elderly group; however, aging significantly decreased acetylcholine or nitroprusside responses when compared to the Young controls (p < 0.02). Furthermore, the ratio between acetylcholine and nitroprusside. a marker of endothelial NO synthase activity, was significantly greater in the young Volunteers (0.816 +/- 0.094% vs. 0.892 +/- 0.146 % vs. 1.389 +/- 0.2%. in atherosclerotic vascular disease, healthy elderly group, and young controls respectively).Conclusions: Forearm blood flow responses to endothelium dependent and independent Stimuli are blunted with aging, independent of the presence of atherosclerotic disease. Moreover, the normal aging process may induce significant global vascular dysfunction (involving the endothelium and the vascular smooth muscle), to as great a degree as clinically manifest atherosclerosis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Objective: Polycystic ovary syndrome (PCOS) is associated with biochemical evidence of early atherosclerosis; however, data regarding vascular function are controversial. We hypothesized that resistance vessel function (mediated by the endothelium or smooth muscle) would be impaired in women with PCOS and aimed to determine the contribution of hyperandrogenism, obesity, or insulin resistance to vascular dysfunction.Design: Prospective study.Setting: University practice.Patient(s): Women with PCOS (n = 24) and age/weight-matched controls (n = 22).Intervention(s): Vascular function was assessed by measuring forearm vasodilation in response to both endothelium-dependent (acetylcholine/bradykinin) and endothelium-independent dilators (nitroprusside/verapamil).Main Outcome Measure(s): Resistance vessel function.Result(s): Forearm vasodilation to all four drugs was reduced (> 50%) in obese PCOS compared to lean PCOS subjects. There was no significant difference in vascular function between obese or lean women with PCOS compared to corresponding controls. Androgen levels did not correlate with vascular function. Stepwise regression analysis showed that body mass index (BMI) contributed maximally to vascular dysfunction (R-2 = 0.47).Conclusion(s): This comprehensive study demonstrates for the first time that obese women with PCOS have markedly reduced vascular smooth muscle function compared to lean subjects with PCOS. In our study obesity and insulin resistance, but not hyperandrogenism, appeared to be significant modulators of vascular function.