Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistant hypertension is defined as blood pressure that remains uncontrolled in spite of >or= 3 antihypertensive medications at effective doses, ideally including a diuretic. Although exact prevalence is unknown, clinical trials suggest that 20% to 30% of study participants are resistant. Hyperaldosteronism, obesity, refractory volume expansion, and obstructive sleep apnea are common findings in resistant hypertension patients. Multiple studies indicate that primary aldosteronism (PA) is common (approximately 20%) in patients with resistant hypertension. Screening for PA is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio. Successful treatment of resistant hypertension is predicated on improvement of lifestyle factors; accurate diagnosis and treatment of secondary causes of hypertension; and use of effective multidrug regimens. A long-acting diuretic, specifically chlorthalidone, is recommended as part of the treatment regimen. Recent studies demonstrate that mineralocorticoid receptor antagonists provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess.
 ...
PMID:Resistant hypertension and hyperaldosteronism. 1895 38

Uncontrolled arterial hypertension is a frequent clinical problem, affecting 1/10 of hypertensive subjects, and can lead to severe renal, cerebral and cardiovascular damage. Common causes of poorly controlled blood pressure include lack of compliance, inadequate antihypertensive medication and white-coat hypertension, all referred to as "false" therapy-resistant hypertension. 4-19% of patients with arterial hypertension suffer from "true" therapy-resistant hypertension: this is defined as failure to achieve target blood pressure values despite full-dose triple drug regimen including a diuretic. In most cases, its etiology is multifactorial. Frequent causes include interfering medication, volume overload, chronic kidney disease, obstructive sleep apnea and secondary causes such as primary aldosteronism. Factors such as obesity, high salt intake and excessive alcohol ingestion contribute to poor blood pressure control. This article reviews the literature and describes epidemiology and etiology of therapy-resistant hypertension.
 ...
PMID:[Epidemiology and etiology of therapy-resistant hypertension]. 1904 88

The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin-angiotensin-aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic beta-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease.
 ...
PMID:Narrative review: the emerging clinical implications of the role of aldosterone in the metabolic syndrome and resistant hypertension. 1948 12

High blood pressure is often difficult to control. Resistant hypertension is blood pressure above goal despite adherence to a combination of at least three antihypertensive medications of different classes, optimally dosed and usually including a diuretic. The approach to blood pressure that is apparently difficult to control begins with an assessment of the patient's adherence to the management plan, including lifestyle modifications and medications. White-coat hypertension may need to be ruled out. Suboptimal therapy is the most common reason for failure to reach the blood pressure goal. Once-daily fixed-dose combination pills may improve control through the synergism of antihypertensive agents from different classes and improved adherence. Truly drug-resistant hypertension is commonly caused by chronic kidney disease, obstructive sleep apnea, or hyperaldosteronism, all of which can lead to fluid retention. Higher doses of diuretics (or a change to a loop diuretic) are usually needed. Other strategies include adding an alpha blocker, alpha-beta blocker, clonidine, or an aldosterone antagonist (e.g., spironolactone). Particularly in patients with diabetes or renal disease, combining a long-acting nondihydropyridine with a dihydropyridine calcium channel . blocker can also be considered. Obesity, heavy alcohol intake, high levels of dietary sodium, and interfering substances (especially nonsteroidal anti-inflammatory drugs) contribute to hypertension that is resistant or difficult to control.
 ...
PMID:Evaluation and management of the patient with difficult-to-control or resistant hypertension. 2070 61

The biochemical and hormonal data in patients with adrenal incidentalomas were evaluated to compare the differences between adrenal adenomas and other benign lesions and to find the relationship between metabolic parameters and adrenal hormones. Ninety two patients (29men, age 20-90 years) with incidentally discovered unilateral or bilateral adrenal masses detected on CT were included in this study for the reasons others than adrenal pathology. Glycemia, cholesterolemia, triglyceridemia, hormonal evaluation including plasma ACTH, plasma aldosterone, plasma renin acitivity, overnight dexametasone test, ACTH test, free plasma metanephrines, urinary catecholamines were determined. In the group of patients with adrenal masses the prevalence of arterial hypertension was three fold higher, the prevalence of DM was approximately five fold higher and the prevalence of the overweight and obesity two fold higher than is reported in the general population. The most frequent adrenal masses were nonfunctional masses, the occurence of functional lesions was as follows: steroid enzymopathies (an exaggerated response of 17-OHP indicating a possible 21-hydroxylase deficiency), subclinical Cushing syndrome, primary aldosteronism and pheochromocytoma (5%, 2%, 2% and 1% respectively). There were no significant differences in evaluated data between patients with adenomas and hyperplasia and also no significant difference in evaluated data between lesions smaller than 3 cm and lesions greater than 3 cm. We did not find any correlations between plasma cortisol and lipid values. In this study we confirmed a higher prevalence of symptoms characteristic for different metabolic syndromes in these patients with adrenal incidentalomas, which indicate systematic screening for the metabolic syndrome including evaluation of the insuline resistance in this patients.
 ...
PMID:Hormonal and metabolic evaluation of adrenal incidentalomas. 2251 94

Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.
 ...
PMID:Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis. 1987 61

Obese persons with metabolic syndrome often have associated with salt-sensitive hypertension, microalbuminuria, and cardiac dysfunction, and the plasma aldosterone level in one-third of metabolic syndrome patients is clearly elevated. Hyperaldosteronism, which may be caused at least partially by certain adipocyte-derived factors, contributes to the development of proteinuria in obese hypertensive rats, and salt loading aggravates the proteinuria and induces cardiac diastolic dysfunction because of inadequate suppression of plasma aldosterone level. However, mineralocorticoid receptor (MR) antagonists prevent salt-induced renal and cardiac damage, suggesting that aldosterone excess and a high-salt diet exert an unfavorable synergistic action on the kidney and heart. In Dahl salt-sensitive rats, however, despite appropriate suppression of plasma aldosterone with a high-salt diet, salt loading paradoxically activated renal MR signaling, and the renal injury was markedly prevented by MR antagonists. Accordingly, we discovered an alternative pathway of MR activation in which Rac1, a small GTP-binding protein, activates MRs. Salt loading activates renal Rac1 in Dahl salt-sensitive rats, and Rac1 in turn induces MR activation, which results in renal injury, and the renal injury has been found to be prevented by Rac1 inhibitors. Moreover, several metabolic syndrome-related factors induce Rac1 activation, and one of them, hyperglycemia, activates MRs via Rac1 activation. Consistent with this, Rac1 inhibitors attenuated the proteinuria and renal injury in obese hypertensive animals. Thus, both salt and obesity activate Rac1 and cause MR activation. Abnormal activation of the aldosterone/MR pathway plays a key role in the development of salt-sensitive hypertension and renal injury in metabolic syndrome.
 ...
PMID:Mineralocorticoid receptors, salt-sensitive hypertension, and metabolic syndrome. 2017 94

The prevalence of diabetes, hypertension, and cardiovascular disease (CVD) and chronic kidney disease (CKD) is increasing in concert with obesity. Insulin resistance, metabolic dyslipidemia, central obesity, albuminuria. and hypertension commonly cluster to comprise the cardiometabolic syndrome (CMS). Emerging evidence supports a shift in our understanding of the crucial role of elevated serum aldosterone in promoting insulin resistance and resistant hypertension. Aldosterone enhances tissue generation of oxygen free radicals and systemic inflammation. This increase in oxidative stress and inflammation, in turn, contributes to impaired insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. In this context, recent investigation indicates that hyperaldosteronism, which is often associated with obesity, contributes to impaired pancreatic beta-cell function as well as diminished skeletal muscle insulin metabolic signaling. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated, in part, by aldosterone's nongenomic as well as genomic signaling through the mineralocorticoid receptor (MR). In the CMS, there are increased circulating levels of glucocorticoids, which can also activate MR signaling in cardiovascular, adipose, skeletal muscle, neuronal, and liver tissue. Furthermore, there is increasing evidence that fat tissue produces a lipid soluble factor that stimulates aldosterone production from the adrenal zona glomerulosa. Recently, we have learned that MR blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation as well as reduces the progression of CVD and CKD. In summary, aldosterone excess exerts detrimental metabolic effects that contribute to the development of the CMS and resistant hypertension as well as CVD and CKD.
 ...
PMID:Aldosterone: role in the cardiometabolic syndrome and resistant hypertension. 2022 58

Obstructive sleep apnoea (OSA) is a sleep disorder characterized by recurrent episodes of oxygen desaturation during sleep, representing an independent risk factor for cardiovascular disease, such as myocardial infarction, stroke, congestive heart failure and resistant hypertension. Several neurohormonal mechanisms have been suggested to account for blood pressure increases, such as sympathetic nervous system hyperactivity, oxidative stress, renin-angiotensin-aldosterone system (RAAS) activation, endothelin system activation, and endothelial dysfunction. The aim of this study was to evaluate the behaviour of RAAS and the presence of primary aldosteronism (PA) in these patients and possible correlations between RAAS and the severity of OSA. From October 2007 to November 2008 we studied 325 consecutive newly diagnosed hypertensive patients; 71 patients (21.8%) presented with clinical signs of sleep disorders, evaluated also through a specific questionnaire (Epworth Sleepiness Scale). In hypertensive patients with sleep disorders, 53 patients were affected by OSA; in this group 18 patients were affected by PA (five with aldosterone-producing adenoma (APA) and 13 with bilateral hyperplasia (IHA)); obesity was also demonstrated (BMI > 30 kg/m(2)). Overall, in patients with OSA PRA levels correlated positively with apnoea/hypopnoea index (AHI; r = 0.35; p<0.01), and in all groups the waist circumference and the neck circumference were correlated positively with AHI (r = 0.3 p<0.02 and r = 0.3 p<0.03, respectively). We revealed a high prevalence of PA in patients with OSA, and we can conclude that patients with hypertension and OSA, especially those who are newly diagnosed, must be evaluated for PA.
 ...
PMID:Renin-angiotensin-aldosterone system in patients with sleep apnoea: prevalence of primary aldosteronism. 2048 24

Key components of the metabolic syndrome (MetS), ie, obesity and insulin resistance, are associated with increased aldosterone production and mineralocorticoid receptor (MR) activation. Both MetS and hyperaldosteronism are proinflammatory and pro-oxidative states associated with cardiovascular disease. This review discusses emerging data that MR activation may contribute to abnormalities seen in MetS. In view of these data, MR antagonists may be beneficial in MetS, not only by controlling hypertension but also by reversing inflammation, oxidative stress, and defective insulin signaling at the cellular-molecular level. Clinical trials have demonstrated benefits of MR antagonists in heart failure, hypertension, and diabetic nephropathy, but additional trials are needed to demonstrate the clinical significance of MR blockade in MetS.
 ...
PMID:Mineralocorticoid receptor antagonists and the metabolic syndrome. 2056 72


<< Previous 1 2 3 4 5 6 7 8 Next >>