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)

Amylin (or islet amyloid polypeptide) has been reported to have binding sites in the central nervous system and the kidney and has been shown to activate plasma renin. It has been postulated that this peptide may be an important mechanistic link between hypertension and diabetes in the insulin resistance syndrome. To explore this issue, the effects of rat amylin on mean arterial blood pressure were investigated in anaesthetised rats. Amylin elicited a pressor response of approximately 10 mmHg (maximal at 100 pmol.kg-1) which was apparent within 30-60 s and persisted over 15 min. At higher concentrations amylin elicited a hypotensive response (negative log IC50 8.52 mol.kg-1). The novel amylin receptor antagonist AC413 (12 nmol.kg-1.min-1) reduced the pressor response but not the hypotensive effects of amylin. The peptide antagonist calcitonin gene-related peptide (CGRP)8-37 (12 nmol.kg-1.min-1) reduced the pressor response elicited by amylin and also antagonized the hypotensive effect of amylin. Pre-treatment of animals with the ganglion blocker mecamylamine (3 mg.kg-1 s.c.) reduced the pressor effect of amylin. Following the administration of the angiotensin converting enzyme inhibitor ramiprilat (300 nmol.kg-1 i.v.) the pressor response to amylin was reduced. Salmon calcitonin also elevated blood pressure in the anaesthetised rat; doses of amylin and salmon calcitonin associated with a pressor effect were associated with increases in plasma renin activity. We conclude that amylin may act centrally to elevate blood pressure in the anaesthetised rat, possibly through activation of the renin angiotensin system.
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PMID:Rat amylin mediates a pressor response in the anaesthetised rat: implications for the association between hypertension and diabetes mellitus. 908 62

Amylin or islet amyloid polypeptide (IAPP) is the protein component of amyloid deposits commonly seen in pancreatic islets of patients with type 2 diabetes mellitus. In in vitro and in animal studies amylin has been shown to decrease insulin secretion and induce insulin resistance. Amylin is stored in the beta-cells and released together with insulin. Circulating amylin is increased in obesity, hypertension and pregnancy, while it is absent in type 1 diabetes mellitus. In type 2 diabetes mellitus the secretion of amylin is impaired prior to that of insulin. Infusion of amylin in man in doses leading to pharmacological levels did not cause any decrease of insulin sensitivity but an impairment of insulin secretion occurred. The recent availability of an amylin antagonist confirmed the effect of amylin on the decrease of insulin secretion in man. The kinetic pattern of amylin, which is presumably excreted by the kidneys, closely resembles that of C-peptide. Subcutaneous administration of the amylin agonist, pramlintide, delays gastric emptying in patients with type 1 diabetes mellitus and, thus, reduces postprandial hyperglycemia. In summary, there is evidence that amylin is able to regulate insulin secretion and gastric emptying in man, but further proof is required.
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PMID:[Amylin/IAPP (islet amyloid polypeptide)--physiology and clinical significance]. 928 Dec 27

High-affinity binding sites for the pancreatic beta-cell hormone amylin have been reported in the kidney, and it has been postulated that these sites may be involved in the genesis of hypertension. In the present study, we have used in vivo injection of 125I-amylin and in vitro autoradiographic techniques to assess renal amylin binding in both a genetic and a surgically induced model of hypertension. In the spontaneously hypertensive rat (SHR) at 6 weeks of age, before the rise in systolic blood pressure, there was a 36% increase in density of amylin binding compared with their normotensive counterpart, the Wistar-Kyoto rat (WKY). In SHR, there was a further increase in the density of amylin binding (to 53% greater) as the systolic blood pressure rose between 6 and 12 weeks of age. Histological examination of kidneys from SHR at 12 weeks of age revealed staining for a brush border glycoprotein, normally restricted to the proximal tubules, extending from the urinary pole into half of the epithelial lining of the glomerular capsule. In contrast to WKY, these cells also bound 125I-amylin with high density in SHR. In a rat model of renal ablation and hypertension, systolic blood pressure correlated with the density of 125I-amylin binding in the renal cortex (r=.54, P=.003, n=28). The changes in amylin binding reported here suggest a possible role for this peptide and/or activation of its receptor in the genesis as well as the maintenance of hypertension.
Hypertension 1997 Sep
PMID:Increased density of renal amylin binding sites in experimental hypertension. 931 32

1. There are high-affinity binding sites for amylin in the renal cortex associated with proximal tubules. These appear to represent seven transmembrane (heptatopic) receptors that are known to form ternary complexes with G-proteins and activate second messenger systems. 2. Amylin stimulates sodium/water reabsorption from the basolateral side of the proximal tubules and plays a role in sodium homeostasis. 3. The transient expression of amylin-like mRNA has been detected perinatally, using in situ hybridization, in the subnephrogenic zone of the metanephros and is associated with proximal tubules of the developing nephron. There it is thought to play a role as a growth factor for brush border epithelial cells in the developing kidney and in renal regrowth in the adult kidney. 4. In two models of hypertension, the spontaneously hypertensive rat (SHR) and one created surgically by subtotal nephrectomy, renal amylin receptors are activated. In the SHR, activation precedes the rise in blood pressure and suggests that activation of the amylin system may be an important event in the development of hypertension.
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PMID:Amylin: physiological roles in the kidney and a hypothesis for its role in hypertension. 975 Sep 52

The range of known actions of amylin are reviewed together with the proposal that an important role for amylin may be the hormonal integration of diverse physiological systems activated with feeding. Major targets for the action of amylin are found within the kidney. Components of the amylin system (AS) have been shown to influence the activity of components of the renin-angiotensin system (RAS), and vice versa, in normal, hypertensive and diabetic models. For instance, amylin injected into humans and rats elicits a rapid rise in plasma renin activity. Furthermore, in two models of hypertension (the spontaneously hypertensive rat (SHR) and the model with subtotal nephrectomy (STNx)), the density of amylin-binding sites in the renal cortex associated with the proximal tubules, was associated with elevation of blood pressure. In normotensive controls and in the STNx model, but not in the SHR model, treatment with angiotensin-converting enzyme (ACE) inhibitors reduced blood pressure and the density of amylin binding in the renal cortex. In Sprague-Dawley rats, angiotensin II (Ang II) infusion was associated with increased density of amylin-binding sites as well as elevated blood pressure. Thus, there appears to be a direct relationship between the activity of Ang II and the binding sites for amylin in the renal cortex. From these studies it has been postulated that the activation of the AS in the kidney may play a role in the genesis and/or development of hypertension in certain contexts. The transient expression of amylin mRNA has been detected perinatally, using in situ hybridization, in the subnephrogenic zone of the metanephros and is associated with proximal tubules of the developing nephron. These cells situated close to the glomeruli, represent a subset of brush border epithelial cells. Amylin immunoreactivity (IR) is also found in these cells and colocalizes with angiotensinogen IR. Thus a second important role for amylin is described in which it plays a role as a growth factor in the developing kidney and in renal regrowth in the adult kidney. In a model of IDDM (streptozotocin diabetes), amylin and angiotensinogen IR are both restricted to a subset of brush border epithelial cells close to glomeruli which, in the developing kidney, expressed amylin mRNA. Thus in this IDDM model, we hypothesize that amylin mRNA transcription which is normally downregulated in the adult, is upregulated in this subset of these brush border epithelial cells, and that it stimulates the activity of a local RAS by an intracellular mechanism, leading to the biosynthesis of Ang II. It remains to be determined that if amylin is playing a role in stimulating local Ang II production at these sites, this provides a mechanism for activation of TGF-beta, ultimately leading to interstitial fibrosis.
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PMID:Interaction of the renal amylin and renin-angiotensin systems in animal models of diabetes and hypertension. 993 Mar 78

Hypertension has been recognized as a risk factor for Alzheimer's disease (AD). Moreover, serum beta-amyloid (A beta) levels are elevated in several mutations linked to familial AD, as well as in some sporadic AD individuals. To determine the in vivo effects of A beta on blood pressure, A beta(1-40) was infused intra-arterially into anesthetized rats. For all animals, strong correlations exist between pre-infusion mean arterial blood pressure (MA beta) and post-arterial infusion increases in blood pressure. In spontaneously hypotensive animals, A beta infusion resulted in substantial increases in MA beta compared to vehicle distilled water infusion. A beta(1-40) was also able to accelerate MA beta return from induced hypotension, but infusion of A beta(1-42), or rat amylin had no such effect. These results provide evidence that circulating A beta(1-40) can exert vasopressor actions in vivo. Moreover, they suggest a pathophysiologic role for vascular A beta in AD that precedes A beta deposition and dementia onset.
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PMID:Intravascular beta-amyloid infusion increases blood pressure: implications for a vasoactive role of beta-amyloid in the pathogenesis of Alzheimer's disease. 1040 67

To evaluate the possible role of insulin, proinsulin, and amylin in the renin-angiotensin system, the direct effect of these peptides on renin release was examined using perfused kidney of rats. Renin release was significantly increased from a basal value of 6.1 +/- 1.8 to a peak value of 10.1 +/- 2.3 ng angiotensin I (Ang I)/mL/h by 0.5 nmol insulin, from 6.0 +/- 1.7 to 16.7 +/- 4.5 ng Ang I/mL/h by 1 nmol insulin, and from 6.1 +/- 1.8 to 18.0 +/- 5.5 ng Ang I/mL/h by 8 nmol insulin. Renin release was not significantly changed by perfusion of 0.05 nmol proinsulin or amylin but significantly increased from a basal value of 6.1 +/- 1.7 to a peak value of 8.1 +/- 3.6 ng Ang I/mL/h by 1 nmol proinsulin, from 5.6 +/- 1.7 to 12.1 +/- 3.8 ng Ang I/mL/h by 8 nmol proinsulin, from 5.7 +/- 1.9 to 8.2 +/- 3.5 ng Ang I/mL/h by 1 nmol amylin, and from 5.2 +/- 2.0 to 12.4 +/- 3.3 ng Ang I/mL/h by 8 nmol amylin. The concentration of cyclic adenosine monophosphate in the effluent was significantly increased from a basal value of 5.1 +/- 1.6 to a peak value of 10.6 +/- 2.5 mmol/min by 8 nmol amylin but not altered by perfusion of insulin or proinsulin. The addition of 0.05 nmol proinsulin and 0.05 nmol of amylin on 0.5 nmol insulin significantly enhanced renin release. These results indicate that insulin may play an important physiologic role in the renin-angiotensin system and suggest that proinsulin and amylin may be involved in the genesis and development of hypertension through enhancement of insulin-stimulated renin release.
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PMID:Effect of insulin, proinsulin, and amylin on renin release from perfused rat kidney. 1143 78

Adrenomedullin is a 52-amino acid peptide that was first isolated from human pheochromocytoma. Subsequently, it was found to be distributed widely in the body, including throughout the cardiovascular system. It belongs to a family of peptides that include calcitonin gene-related peptide and amylin. Adrenomedullin causes vasorelaxation and influences vascular proliferation and interacts closely with nitric oxide, and it may have a role in the pathophysiology of hypertension, ischemic heart disease, and cardiac and renal failure. Nonpeptide agonists or antagonists of adrenomedullin may have potential therapeutic application. The role of adrenomedullin in septicemic shock also merits further investigation.
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PMID:Adrenomedullin: its role in the cardiovascular system. 1547 33

Obesity represents the most prevalent nutritional problem worldwide which in the long run predisposes to development of diabetes mellitus, hypertension, endometrial carcinoma, osteoarthritis, gall stones and cardiovascular diseases. Despite significant reductions in dietary fat consumption, the prevalence of obesity is on a rise and is taking on pandemic proportions. Obesity develops when energy intake exceeds energy expenditure over time. Recently, a close evolutionary relationship between the peripheral and hypothalamic neuropeptides has become apparent. The hypothalamus being the central feeding organ mediates regulation of short-term and long-term dietary intake via synthesis of various orexigenic and anorectic neuropeptides. The structure and function of many hypothalamic peptides (neuropeptide Y (NPY), melanocortins, agouti-related peptide (AGRP), cocaine and amphetamine regulated transcript (CART), melanin concentrating hormone (MCH), orexins have been characterized in rodent models The peripheral neuropeptides such as cholecystokinin (CCK), ghrelin, peptide YY (PYY3-36), amylin, bombesin regulate important gastrointestinal functions such as motility, secretion, absorption, provide feedback to the central nervous system on availability of nutrients and may play a part in regulating food intake. The pharmacological potential of several endogenous peripheral peptides released prior to, during and/or after feeding are being explored. Long-term regulation is provided by the main circulating hormones leptin and insulin. These systems implicated in hypothalamic appetite regulation provide potential targets for treatment of obesity which could potentially pass into clinical development in the next 5 years. This review summarizes various effects and interrelationship of these central and peripheral neuropeptides in metabolism, obesity and their potential role as targets for treatment of obesity.
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PMID:Role of neuropeptides in appetite regulation and obesity--a review. 1693 29

1. Differences in blood lipids, glucose, insulin, amylin, adrenocorticotropic hormone (ACTH), cortisol, aldosterone, angiotensin II, metabolites of nitric oxide (nitrate, nitrite), asymmetric dimethyl arginine, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, C-reactive protein, homocysteine and oxidative status (urate, vitamin A, vitamin E, beta-carotene and total anti-oxidant capacity) were investigated in men (aged 18-25 years) with (+) or without (-) a family history (FH) of hypertension. 2. In the present study, FH+ was defined as having at least one parent or grandparent taking medication for hypertension. Blood (60 mL) was sampled (0800-1000 hours) from a cannulated forearm vein after an overnight fast and 24 h abstinence from caffeine-containing products and alcohol. 3. Comparing FH+ with FH-, systolic blood pressure (124 +/- 1 vs 117 + 3 mmHg, respectively; n = 50 and 14, respectively; P < 0.05) and plasma cortisol (377 +/- 23 vs 298 +/- 24 nmol/L, respectively; n = 43 and 12, respectively; P < 0.05) were found to be significantly higher in the former group. 4. No significant difference was found between the two groups for body mass index, resting heart rate, diastolic and mean blood pressures or any of the biochemical measures studied. 5. A significant correlation was found between cortisol and ACTH (r = 0.73). No correlation was found between cortisol and any other parameter measured. 6. These data indicate that elevated cortisol levels are characteristic of young lean normotensive FH+ men. The future impact of this on their vascular health and hypertension remains to be determined.
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PMID:Elevated levels of circulating cortisol in young normotensive adult men with a family history of hypertension. 1806 96


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