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)

Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD) is rapidly changing. Cellular pathways that involve the polycystins are being mapped and involve the primary cilium, intracellular calcium and cAMP regulation, and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging approaches, earlier diagnosis of hepatic cystic disease is possible, and measurement of kidney and cystic growth as well as kidney blood flow is possible over relatively short periods. PKD gene type, gender, proteinuria, and the presence of hypertension relate to the rate of kidney growth in ADPKD. On the basis of risk factors for progression to ESRD and the pathogenic roles that intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being tested, including maximal inhibition of the renin-angiotensin system, inhibition of renal intracellular cAMP using vasopressin V2 receptor antagonists, and somatostatin analogues, as well as inhibitors of mTOR. This review addresses the current understanding of the pathogenesis and the natural history of ADPKD; accuracy and reliability of diagnostic approaches in utero, childhood, and adulthood; the value of reliable magnetic resonance imaging to measure disease progression early in the course of ADPKD; and novel therapeutic approaches that are being evaluated in ADPKD.
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PMID:Autosomal dominant polycystic kidney disease: time for a change? 1742 47

Essential hypertension is a complex disease with both genetic and environmental determinants. The effect of spontaneous hypertension on the distribution and occurrence of somatostatin-, gastrin- and serotonin-immunoreactive cells in the fundus and pylorus of the rat stomach was examined by immunohistochemistry. The animals were killed by decapitation at 4 and 16 weeks of age (5 control rats and 5 hypertensive rats). Endocrine cells generally increase in number in hypertensive rats as compared to control rats. However, the detailed responses of endocrine cells to hypertension depend on the cell type, region of gastric mucosa and age of animals. The present results suggest that hypertension has an influence on the intrinsic regulatory system by endocrine cells control in the rat stomach.
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PMID:An immunohistochemical study of endocrine cells in the stomach of hypertensive rats. 1792 43

Aminopeptidase N (APN) or CD13 is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes. APN is abundant in the kidneys and central nervous system. Identified substrates include Angiotensin III (Ang III); neuropeptides, including enkephalins and endorphins; and homones, including kallidan and somatostatin. It is developmentally expressed, a myelomonocytic marker for leukemias, and a receptor for coronovirus. There is evolving support for APN in the regulation of arterial blood pressure and the pathogenesis of hypertension. In rodent strains, intracerebraventricular (i.c.v.) infusions of APN reduces, while inhibitors of APN activity have a pressor effect on blood pressure. Dysregulation of central APN has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat. There is evidence that renal tubule APN inhibits Na flux and plays a mechanistic role in salt-adaptation. A functional polymorphism of the ANP gene has been identified in the Dahl salt-sensitive rat. Signaling by APN impacting on blood pressure is likely mediated by regulation of the metabolism of Ang III to Ang IV. Whether APN regulates arterial blood pressure in humans or is a therapeutic target for hypertension are subjects for future exploration.
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PMID:Aminopeptidase N in arterial hypertension. 1800 60

Polycystic kidney diseases (autosomal dominant and autosomal recessive) are progressive renal tubular cystic diseases, which are characterised by cyst expansion and loss of normal kidney structure and function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common life- threatening, hereditary disease. ADPKD is more prevalent than Huntington's disease, haemophilia, sickle cell disease, cystic fibrosis, myotonic dystrophy and Down's syndrome combined. Early diagnosis and treatment of hypertension with inhibitors of the renin-angiotensin-aldosterone system (RAAS) and its potential protective effect on left ventricular hypertrophy has been one of the major therapeutic goals to decrease cardiac complications and contribute to improved prognosis of the disease. Advances in the understanding of the genetics, molecular biology and pathophysiology of the disease are likely to facilitate the improvement of treatments for these diseases. Developments in describing the role of intracellular calcium ([Ca(2+)](i)) and its correlation with cellular signalling systems, Ras/Raf/mitogen extracellular kinase (MEK)/extracellular signal-regulated protein kinase (ERK), and interaction of these pathways with cyclic adenosine monophosphate (cAMP) levels, provide new insights on treatment strategies. Blocking the vasopressin V(2) receptor, a major adenylyl cyclase agonist, demonstrated significant improvements in inhibiting cytogenesis in animal models. Because of activation of the mammalian target of rapamycin (mTOR) pathway, the use of sirolimus (rapamycin) an mTOR inhibitor, markedly reduced cyst formation and decreased polycystic kidney size in several animal models. Caspase inhibitors have been shown to decrease cytogenesis and renal failure in rats with cystic disease. Cystic fluid secretion results in cyst enlargement and somatostatin analogues have been shown to decrease renal cyst progression in patients with ADPKD. The safety and efficacy of these classes of drugs provide potential interventions for experimental and clinical trials.
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PMID:Potential pharmacological interventions in polycystic kidney disease. 1803 88

Diabetic retinopathy continues to be the leading cause of legal blindness among working-age individuals. The earliest histological features of diabetic retinopathy include neuroretinal damage, capillary basement membrane thickening, loss of pericytes and loss of endothelial cells. At advanced stages, neovascularization, the hallmark of proliferative diabetic retinopathy (PDR) occurs, and blindness can result from relentless abnormal fibrovascular proliferation with subsequent bleeding and retinal detachment. Macular oedema is another retinal complication of diabetes that is responsible for a major part of vision loss, particularly in type 2 diabetes. The breakdown of the blood retinal barrier and the consequent vascular leakage and thickening of retina are the main events involved in its pathogenesis. Although a tight control of both blood glucose levels and hypertension are essential to prevent or arrest progression of the disease, the recommended goals are difficult to achieve in many patients. Laser photocoagulation treatment soon after the onset of PDR significantly reduces the incidence of severe vision loss. However, the optimal timing for laser treatment is frequently passed and, in addition, it is not uniformly successful in halting visual decline. For all these reasons, new pharmacological treatments based on the understanding of the pathophysiological mechanisms of diabetic retinopathy have been developed in recent years. There is mounting evidence to suggest that angiogenic factors play a crucial role in PDR development, vascular endothelial growth factor (VEGF) being the most relevant. Other growth factors or cytokines such as insulin-like growth factor I (IGF-1), hepatocyte growth factor (HGF), basic fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), pro-inflammatory cytokines and angiopoetins, are also involved in the pathogenesis of PDR. However, the intraocular synthesis of angiogenic factors is counterbalanced by the synthesis of antiangiogenic factors. Therefore, the balance between the angiogenic and antiangiogenic factors rather than angiogenic factors themselves will be crucial in determining the progression of PDR. The main antiangiogenic factor is the pigment epithelium derived factor (PEDF) but the transforming growth factor beta (TGF-beta), thrombospondin (TSP) and somatostatin are also among the intraocullary synthesized antiangiogenic factors.
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PMID:Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. 1822 Jun 19

We have previously shown that the endocrine cells in the stomach increase in number in spontaneously hypertensive rats (SHR) that suggests that the hypertension has an influence on the intrinsic regulatory system by endocrine cells control in the stomach of rats. The aim of the present study is to find differences in the density of neuroendocrine (NE) cells of stomach rats and composition in doxazosin treated SHR compared to untreated animals. Fragments of the pyloric region were collected at 12 weeks of age. Paraffin-embedded sections were stained with H+E and by silver impregnation. To identify NE cells, immunohistochemical reaction (IR) was performed with the use of a specific antibody against somatostatin, gastrin, serotonin and chromogranin. It was revealed that the distribution density of IR-endocrine cells all searched types was considerable lower in the pyloric mucosa of hypertension animals treated with doxazosin compared to SHR untreated and was on level healthy rats. The present study demonstrated that doxazosin inhibit the hypertension-induced changes of endocrine cells in the stomach of SHR.
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PMID:Can doxazosin inhibit the hypertension-induced changes of endocrine cells in the stomach of spontaneously hypertensive rats? 1844 98

Polycystic kidney disease is an inherited multisystem disorder. It causes progressive loss of kidney function, flank pain, urinary tract infection, arterial hypertension and vascular abnormalities. Until the present time the treatment of polycystic kidney disease has been symptomatic. New approaches based on cell culture of cyst wall epithelia and on the discovery of polycystins 1 and 2 have lead to novel treatment protocols to attack the origin of the disease. These protocols involve vasopressin antagonists, rapamycin and somatostatin at the present time.
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PMID:Polycystic kidney disease: will it become treatable? 1861 80

The aim of the present study is to provide a review of the expression and action of trophic factors in the carotid body. In glomic type I cells, the following factors have been identified: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, artemin, ciliary neurotrophic factor, insulin-like growth factors-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha and -beta1, interleukin-1beta and -6, tumour necrosis factor-alpha, vascular endothelial growth factor, and endothelin-1 (ET-1). Growth factor receptors in the above cells include p75LNGFR, TrkA, TrkB, RET, GDNF family receptors alpha1-3, gp130, IL-6Ralpha, EGFR, FGFR1, IL1-RI, TNF-RI, VEGFR-1 and -2, ETA and ETB receptors, and PDGFR-alpha. Differential local expression of growth factors and corresponding receptors plays a role in pre- and postnatal development of the carotid body. Their local actions contribute toward producing the morphologic and molecular changes associated with chronic hypoxia and/or hypertension, such as cellular hyperplasia, extracellular matrix expansion, changes in channel densities, and neurotransmitter patterns. Neurotrophic factor production is also considered to play a key role in the therapeutic effects of intracerebral carotid body grafts in Parkinson's disease. Future research should also focus on trophic actions on carotid body type I cells by peptide neuromodulators, which are known to be present in the carotid body and to show trophic effects on other cell populations, that is, angiotensin II, adrenomedullin, bombesin, calcitonin, calcitonin gene-related peptide, cholecystokinin, erythropoietin, galanin, opioids, pituitary adenylate cyclase-activating polypeptide, atrial natriuretic peptide, somatostatin, tachykinins, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.
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PMID:Trophic factors in the carotid body. 1877 56

Bulbospinal neurons in the rostral ventrolateral medulla (RVLM) are critical for the maintenance of sympathetic vasomotor tone and normal cardiovascular reflex function. So far, selectively eliminating/inhibiting distinct subpopulations of RVLM neurons has not significantly altered arterial pressure. Here we show that RVLM presympathetic neurons that express somatostatin 2A receptors are essential for maintaining and potentially generating sympathetic vasomotor tone. Combined immunocytochemistry and in situ hybridization were used to map the expression of somatostatin receptors 1, 2A, 2B, 3, and 4 (sst1 through 4, respectively) in the rat RVLM. sst1 and sst2B were absent; sst3 and sst4 were sparse. However, sst2A was found postsynaptically and detected in 35+/-5% of bulbospinal RVLM neurons a population that included 54+/-4% of catecholaminergic and 30+/-3% of enkephalinergic neurons. Bilateral microinjection into the RVLM of either somatostatin or the receptor-selective agonist lanreotide evoked dramatic, dose-dependent sympathoinhibition, hypotension, and bradycardia that were blocked by the sst2 receptor antagonist BIM-23627 in anesthetized rats. Bilateral RVLM microinjection of somatostatin also attenuated chemoreceptor and somatosympathetic reflex function. Somatostatin only eliminated the first sympathoexcitatory peak evoked by somatosympathetic reflex activation, whereas muscimol abolished both excitatory peaks providing functional evidence that the activity of only a subpopulation of RVLM presympathetic neurons is inhibited by somatostatin. We suggest that the subpopulation of bulbospinal RVLM neurons that expresses the sst2A receptor sets sympathetic vasomotor output. These neurons are essential for maintaining resting blood pressure under anesthesia and contribute to adaptive reflexes mediated through the RVLM.
Hypertension 2008 Dec
PMID:Somatostatin 2A receptor-expressing presympathetic neurons in the rostral ventrolateral medulla maintain blood pressure. 1900 Nov 89

The secondary occurrence of type 2 diabetes with various hormonal diseases (e.g. pituitary, adrenal and/or thyroid diseases) is a recurrent observation. Indeed, impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with acromegaly and hypercortisolism (Cushing syndrome). The increased cardiovascular morbidity and mortality associated with acromegaly and Cushing syndrome may partly be a consequence of increased insulin resistance that normally accompanies hormone excess. Acromegalic patients are insulin resistant, both in the liver and in the periphery, displaying hyperinsulinemia and increased glucose turnover in the basal post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is reported to range 16-56%, whereas the degree of glucose tolerance seems correlated with circulating growth hormone (GH) levels, age, and disease duration. Moreover, a family history of diabetes and concomitant presence of arterial hypertension have been found to predispose to diabetes as well. GH has physiological effects on glucose metabolism, stimulating gluconeogenesis and lipolysis, which results in increased blood glucose and free fatty acid levels. Conversely, insulin-like growth factor 1 (IGF-I) enhances insulin sensitivity primarily on skeletal muscles. However, in acromegaly, increased IGF-I levels are unable to counteract the insulin-resistance status determined by GH excess. Therapy with somatostatin analogues (SSAs) induce control of GH and IGF-I excess in the majority of patients, but their inhibitory effect on pancreatic insulin secretion might complicate the overall effect of this treatment on glucose tolerance. Hypercortisolism produces visceral obesity, insulin resistance, and dyslipidemia that together with hypertension, hypercoagulability, and ventricular morphologic and functional abnormalities increase cardiovascular risk, and persist up to 5 years after resolution of hypercortisolism. Hypercortisolism leads to hyperglycaemia and reduced glucose tolerance, determines insulin resistance, stimulates hepatic gluconeogenesis and glicogenolisis. In Cushing syndrome the prevalence of diabetes varies between 20 and 50%, but probably this prevalence is underestimated, as not always an oral glucose tolerance test is performed in the presence of an apparently normal fasting glycaemia. Again, disease duration, rather than hormone levels, seems to be the major determinant in the occurrence of systemic complications in Cushing syndrome. Due to the impact they have on mortality and morbidity in both acromegaly and Cushing syndrome, these complications should be treated aggressively. In patients with neuroendocrine tumours (NETs) the occurrence of altered glucose tolerance may be due to a decreased insulin secretion, like it happens in patients who underwent pancreatic surgery and in those with pheochromocytoma, or to an altered counterbalance between hormones, such as in patients with glucagonoma and somatostatinoma. Moreover, SSAs represent a valid therapeutic choice in the symptomatic treatment of NETs, and also in this case the medical therapy of the primary disease, may have a significant impact on the prevalence of glucose metabolism imbalance. In thyroid disorders, an abnormal glucose tolerance may be principally encountered in hyperthyroidism. The pathogenesis is complex and scant data on prevalence and severity are found in the literature. Adequate treatment for glucose imbalance is mandatory in these peculiar patients in line with the American Diabetes Association and the European Association for the Study of Diabetes consensus statement. In particular, since traditional insulins have two features that may complicate therapy (absorption profiles, delayed onset of action and peak activity), the new insulin analogues could be of particular interest in the management of the secondary diabetes associated with endocrinopathies, considering the frailty of these patients. Indeed, it has been demonstrated that insulin glargine, given once daily, reduces the risk of hypoglycaemia compared with other formulations, and can facilitate a more aggressive insulin treatment in this class of patients.
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PMID:Secondary diabetes associated with principal endocrinopathies: the impact of new treatment modalities. 1932 13


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