Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.
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PMID:Systemic complications of acromegaly: epidemiology, pathogenesis, and management. 1476 29

The pronounced pharmacodynamic effects of human urotensin-II (U-II), a 'somatostatin-like' cyclic undecapeptide, are mediated via the G protein-coupled receptor UT (formerly known as GPR14). Emerging clinical studies implicate U-II in the etiology of several cardiorenal and metabolic disease states in humans. Although the specific pathogenic role(s) of U-II remain to be clearly defined, existing data warrant further clinical investigation. The therapeutic development of specific U-II/UT inhibitors will assist in establishing a causative role for U-II in the progression and/or maintenance of hypertension, heart failure, renal tubular disease and diabetes.
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PMID:Urotensin-II as a novel therapeutic target in the clinical management of cardiorenal disease. 1508 93

The identification of a human homolog of urotensin-II (U-II) and a novel, specific G-protein-coupled receptor by Ames et al. in 1999 changed the perception that the U-II isopeptide family was an esoteric collection of 'somatostatin-like neuropeptides' present only in the nervous systems of an eclectic array of aquatic invertebrates, fish and amphibians. In this article, we review recent developments in the pharmacology of human U-II, focusing on the actions of this peptide in the mammalian cardiorenal system. The putative role of U-II in the etiology of hypertension, heart failure, renal dysfunction and diabetes is discussed, as are novel U-II receptor antagonists.
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PMID:From 'gills to pills': urotensin-II as a regulator of mammalian cardiorenal function. 1510 93

Non-iatrogenic anatomical findings at autopsy provide insight into preterm infant physiology. The different patterns of lipid accumulation in the adrenal may correspond to long-term differences in stress response. Cardiac papillary muscle infarction occurs with asphyxia or shock and can explain myocardial dysfunction. Underdevelopment of preterm kidneys may correlate with susceptibility to renal disease and hypertension in adult life. Immaturity of the lung or immature responses to inflammation, rather than high oxygen concentrations or high ventilation pressures, may underlie chronic lung disease in premature infants. Hepatic extramedullary haematopoiesis is normal but, if excessive or abnormally persistent, can be an indicator of fetal disease. Hypertrophic somatostatin islet cells found with intra-uterine growth retardation may correlate with low serum insulin. Thymic involution may mark the degree of stress. Small thyroglobulin stores may limit the premature neonate's initiation of thermogenesis.
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PMID:Non-iatrogenic pathology of the preterm infant. 1525 Nov 45

Hyperinsulinemia and insulin resistance frequently coexist and have been implicated in the pathogenesis of hypertension. This study aimed to identify the specific effect of hyperinsulinemia on blood pressure and nitric oxide (NO) release in fructose-induced hyperinsulinemic, insulin-resistant rats. Male Sprague-Dawley rats were fed either standard chow or a 60% fructose-enriched diet for 8 weeks before acute study. After basal period, somatostatin (1.3 microg/kg/min) and a variable glucose infusion (to maintain euglycemia) were given intravenously to all groups of rats. In control rats (C) and fructose-fed rats (F) with insulin infusion, insulin (4 mU/kg/min) was given to create a similar hyperinsulinemic condition. In C and F without insulin infusion, a vehicle instead of insulin was infused to produce a hypoinsulinemic state. In C, somatostatin reduced plasma insulin level but did not alter mean arterial pressure (MAP) and heart rate. Insulin infusion significantly increased MAP and NOx (sum of nitrate and nitrite) levels after 90 min and thereafter the elevated MAP and NOx responses were sustained throughout the study. In the basal period, F exhibited significantly higher MAP and plasma insulin levels than C. The index of insulin sensitivity (M) was significantly lower in F than in C with insulin infusion. Somatostatin significantly reduced plasma insulin level but did not affect MAP and NOx level in F. The stimulatory effects of insulin on MAP and NO levels were significantly smaller in F than in C. In conclusion, acute insulin-induced pressor response and NO release were attenuated in rats with fructose-treated insulin resistance, suggesting that hyperinsulinemia-associated attenuation of NO production contributes, at least partly, to the development of fructose-induced hypertension in rats.
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PMID:Attenuation of insulin-mediated pressor effect and nitric oxide release in rats with fructose-induced insulin resistance. 1532 66

Urotensin II (UII) has been found to be a potent vasoactive peptide in humans and in a number of relevant animal models of cardiovascular disease such as the mouse, rat and other non-human primates. This peptide with structural homology to somatostatin was first isolated from the urophysis of fish and was recently found to bind to an orphan receptor in mouse and human. Initially found to have potent vasoconstrictive activities in a variety of vessels from diverse species, it has also been shown to exert vasodilatation in certain vessels in the rat and human by various endothelium-dependent mechanisms. The various vasoactive properties of UII suggest that the peptide may have a physiological role in maintaining vascular tone and therefore may have a role in the pathophysiology of a number of human diseases such as heart failure. Moreover, UII has also been implicated as a mitogen of vascular smooth muscle cells suggesting a deleterious role in atherosclerosis and coronary artery disease. In addition, there is evidence to demonstrate that UII has multiple metabolic effects on cholesterol metabolism, glycemic control and hypertension and therefore may be implicated in the development of insulin resistance and the metabolic syndrome.
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PMID:Urotensin II and cardiovascular diseases. 1547 47

This short review summarizes the results of treatments now available in Italy for the management of GH and IGF-I excess due to primary pituitary somatotroph adenoma, which accounts for over 99% of cases of acromegaly. Goals of treatment of acromegaly should now include, in addition to the reduction of tumor bulk and symptomatic relief, the lowering of GH circulating concentrations to below a critical level (2.5 microg/l, "safe" GH), the normalization of serum IGF-I concentrations according to age, improvement (or at least not worsening) of co-morbidities (diabetes mellitus, hypertension, cardiomyopathy, sleep-apnea), the decrease of the risk of premature mortality. Surgery, radiation (fractionated conventional radiotherapy and radiosurgery) and medical treatments with dopamine agonists and somatostatin analogs are the available options that are discussed in detail. The treatment of acromegaly must be tailored to the needs of the individual patient. Age, tumor size and invasiveness, GH concentrations, the patient's general medical conditions, presence and severity of co-morbidities, availability of local resources such as an expert neurosurgeon or gamma-knife radiosurgery, and of course the informed wishes of the patient are all factors that must be taken into account. For most patients the treatment will be multimodal. However, despite criteria and guidelines based on continuously emerging information about the management of acromegaly, patient outcomes are still less than desirable, with 10 to 20% of patients with uncontrolled disease, despite the use of all available therapies. This underscores the need for the quick introduction in clinical practice of the new therapies.
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PMID:Therapy for the syndromes of GH excess. 1549 58

Regardless of etiology, all cases of endogenous Cushing's syndrome are due to increased production of cortisol by the adrenal gland. Most are caused by adrenocorticotrophic hormone (ACTH)-secreting pituitary adenomas. Alternatively, the glucocorticoid excess may be due to adrenal neoplasia or to ectopic ACTH-secreting tumors. Cushing's syndrome is characterized by endocrine and metabolic alterations such as truncal obesity, hypertension, weakness, amenorrhea, hyperglycemia, osteoporosis and depression. Unless treated, the disease is associated with high morbidity, and ultimately, mortality. Depending on the etiology of Cushing's syndrome two different treatment modalities are possible: reduction of pituitary ACTH production or reduction of adrenocortical cortisol secretion. In the absence of efficient drug therapy, transsphenoidal resection of the pituitary adenoma is the primary treatment of choice for the reduction of ACTH secretion. In the last years there was much progress in understanding the molecular mechanisms that control the function of the hypothalamic-pituitary-adrenal axis. Thus, new insights made it possible to identify potential drug targets for the treatment of Cushing's syndrome. The present article reviews different drug targets and therapeutic options including drugs that control the central ACTH regulation, e.g. by modulating signaling pathways and transcriptional regulation of ACTH biosynthesis, corticotrophin releasing hormone (CRH) or glucocorticoid receptor antagonists, inhibitors of glucocorticoid synthesis, ketoconazole, somatostatin and dopamine analogs. Some of these substances might be useful for the treatment of Cushing's syndrome.
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PMID:New perspectives in the treatment of Cushing's syndrome. 1557 85

Active acromegaly is associated with significant comorbidity and reduced quality of life. However, the prevalence of comorbidity after long-term remission is not established. Therefore, we assessed the presence of comorbidity in 118 patients in long-term remission after surgery, radiotherapy, and/or somatostatin analog treatment according to strict biochemical criteria of serum GH and IGF-I concentrations and evaluated the impact of comorbidity on quality of life. The mean duration of remission was 12.0 +/- 7.4 yr, and mean actual IGF-I sd scores were 0.6 +/- 1.7. Self-reported joint problems occurred in 77% of patients, hypertension in 37%, a history of myocardial infarction in 9%, and diabetes mellitus in 11%. The presence of joint problems was not related to GH and IGF-I levels, active disease duration, or age. Joint complaints had significant negative impact on quality of life. Patients with a history of myocardial infarction had reduced scores for general health, depression, and fatigue, and diabetes mellitus was associated with reduced scores for anxiety and sleep. In conclusion, acromegalic patients had a high prevalence of joint-related comorbidity and hypertension despite long-term control of GH excess. Especially, joint complaints contributed to a reduced perceived quality of life in these patients.
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PMID:Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life. 1574 Dec 57

Urotensin II is the most potent vasoconstrictor known. Paradoxically, urotensin II also possesses vasodilator activity in certain vascular beds. While much is still to be learnt regarding urotensin II's actions on vascular tone, it is now clear that it mediates its effects by interacting with a specific G-protein-coupled receptor. The presence of urotensin II and its receptor in both vertebrate and invertebrate species suggests an evolutionarily conserved role in normal physiology although evidence is mounting for both species-specific as well as disease-specific effects of this peptide. This somatostatin-like peptide was originally thought to reside solely in compartments of the central nervous system. However, recent evidence implicated urotensin II in the pathogenesis of a variety of disease processes ranging from hypertension to hepatic cirrhosis. Increased expression of this peptide has been noted in cardiac, renal and hepatic disease. While the contribution of urotensin II to these diseases remains unclear, the advent of urotensin II antagonists allows for not only the possibility of a new range of therapeutic drugs but also new avenues of investigation and further mechanistic insights into the pathophysiology of these disease processes.
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PMID:Urotensin II: a vascular mediator in health and disease. 1585 35


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