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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-resistance is associated with a number of disease states such as diabetes, syndrome X, and hypertension. These situations may be coupled to insulin-resistance through the insulin signaling system as a common pathway. The purpose of this study was to investigate the receptor binding alterations in streptozotocin-induced diabetic rats, spontaneously hypertensive rats and aortocaval shunted rats (eccentric cardiac hypertrophy). A physical model describing a 1:1 stoichiometry of ligand binding with its receptor is proposed describing reversible binding of [(125)I]insulin or [(125)I]IGF-1 at the microvascular endothelial as well as with the cardiac myocytes after CHAPS-treatment. Analysis of the collected effluents are curve-fitted with a conservation equation and a first-order Bessel function which allowed the calculation of the forward binding constants (k(n)), the reversible constants (k(-n)), the dissociation constants (k(d)) and the residency time constants (tau). The results showed that streptozotocin-induced diabetic rats showed insulin-resistance through alterations in the kinetics of insulin receptor binding. The normotensive controls of the spontaneously hypertension rats (SHR) carry themselves insulin-resistant receptors whose binding to insulin worsens in the hypertensive SHR. Negative cooperativity between insulin-like growth factor IGF-1 and insulin receptors could be a causative factor predisposing for insulin-resistance in the aortocaval shunted rats to insulin resistance. The defects may be occurring at the receptor level in insulin-dependent diabetes mellitus, Wistar-Kyoto rats and spontaneously hypertensive rats. In conclusion, alterations in the kinetics of insulin binding to its receptor seem to play a central role for the initiation of insulin-resistance during the various pathophysiological states.
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PMID:Characterization of insulin-resistance: role of receptor alteration in insulin-dependent diabetes mellitus, essential hypertension and cardiac hypertrophy. 1103 73

Sgk (serum- and glucocorticoid-induced protein kinase) is a serine/threonine-specific protein kinase that is transcriptionally regulated by serum, glucorticoids, and mineralocorticoids. Sgk regulates the amiloride-sensitive sodium channel in kidney principal cells. Insulin and insulin-like growth factor-1 stimulate activity of Sgk by a mechanism mediated by phosphoinositide-dependent kinases (PDK)-1 and -2. In this study, we demonstrate that incubation of transfected cells with 8-(4-chlorophenylthio)-cAMP (8CPT-cAMP; 0.2 mm) led to a 2-fold activation of recombinant Sgk expressed in COS7 cells. Furthermore, the combination of insulin plus 8CPT-cAMP elicited a larger response than either agent alone. The effect of insulin was inhibited by wortmannin (100 nm), but not by the cyclic AMP-dependent protein kinase (PKA) inhibitor, H89 (10 microm). As expected, the effect of 8CPT-cAMP was completely blocked by H89. Surprisingly, the effect of 8CPT-cAMP was also inhibited by wortmannin, suggesting that phosphorylation of Sgk by PDK-1 and/or -2 is required for activation by 8CPT-cAMP. Mutational analysis led to similar conclusions. The Thr(369) --> Ala mutant, lacking the PKA phosphorylation site, was activated by insulin but not 8CPT-cAMP. In contrast, the Ser(422) --> Ala mutant, lacking a PDK-2 phosphorylation site, was inactive and resistant to activation by either insulin or 8CPT-cAMP. In summary, Sgk is subject to complex regulatory mechanisms. In addition to regulation at the level of gene expression, the enzymatic activity of Sgk is regulated by multiple protein kinases, including PKA, PDK-1, and PDK-2. Cross-talk among these signaling pathways may play an important role in the pathogenesis of the hypertension associated with hyperinsulinemia, obesity, and insulin resistance.
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PMID:Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. 1109 81

Increased pressure load and neurohumoral activation are main factors involved in pathomechanism of left ventricular hypertrophy (LVH) in hypertension (HT). To gain insight into the involvement of neurohumoral factors responsible for cardiac hypertrophy, plasma level of aldosterone (Aldo), plasma renin activity (PRA), insulin-like growth factor-1 (IGF-1), pro-endothelin-1 (pro-ET) and atrial natriuretic peptide (ANP) were measured in HT patients (pts) and compared between pts with and without LVH. Also relationships between neurohormones and LV mass index (LVMI), mean blood pressure (MBP) were assessed separately in HT pts with and without LVH. 121 HT patients (pts) of age 17-79 (mean 48 +/- 15.3) were divided into three groups: 1-53 pts with mild HT, 2-44 pts with moderate HT and 3-24 pts with severe HT. Each of the group was divided into pts with and without LVH further all HT pts were divided into two groups; with and without LVH. Control group consisted of 39 healthy normotensives. LV mass was assessed echocardiographically and plasma levels of IGF-1, PRA, Aldo, pro-ET, and ANP were measured by radioimmunoassay in each pts and controls. LVH was found in 35.8% pts with mild HT, in 68.18% pts with moderate HT and in 100% pts with severe HT. The level of all measured neurohormones were significantly higher in pts with LVH compared to pts without LVH (p < 0.001). In pts with LVH there was significant correlation between LVMI and IGF-1, PRA, Aldo, pro-ET-1 and ANP, contrary to pts without LVH in which such correlations was not found. In pts with LVH there was also significant correlation between MBP and IGF-1, PRA, ANP and pro-ET-1. Increased plasma level of PRA, Aldo, IGF-1, pro-ET-1 and ANP in HT pts with LVH and significant correlation between measured neurohormones and LVMI suggests their contribution to LVH in HT pts. Significant correlation between LVMI, MBP and IGF-1 level, PRA and ANP indicate interplay between hemodynamic and neuroendocrine factors in pathomechanism of LVH.
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PMID:[Neurohumoral factors in hypertensive patients with and without left ventricular hypertrophy]. 1123 55

The discovery of a link between in utero experience and later metabolic and cardiovascular disease is one of the most important advances in epidemiology research of recent years. There is increasing evidence that alterations in the fetal environment may have long-term consequences on cardiovascular, metabolic, and endocrine pathophysiology in adult life. This process has been termed programming, and we have shown that undernutrition of the mother during gestation leads to programming of hyperphagia, obesity, hypertension, hyperinsulinemia, and hyperleptinemia in the offspring. Using this model of maternal undernutrition throughout pregnancy combined with postnatal hypercaloric nutrition of the offspring, we examined the effects of IGF-I therapy. Virgin Wistar rats (age 75 +/- 5 d, n = 20 per group) were time mated and randomly assigned to receive food either ad libitum or 30% of ad libitum intake (UN) throughout pregnancy. At weaning, female offspring were assigned to one of two diets (control or hypercaloric [30% fat]). Systolic blood pressure was measured at day 175 and following infusion with 3 microg/g per day recombinant human IGF-1 (rh-IGF-I) by minipump for 14 d. Before treatment, UN offspring were hyperinsulinemic, hyperleptinemic, hyperphagic, obese, and hypertensive on both diets, compared with ad libitum offspring and this was exacerbated by hypercaloric nutrition. IGF-I treatment increased body weight in all treated animals. However, systolic blood pressure, food intake, retroperitoneal and gonadal fat pad weights, and plasma leptin and insulin concentrations were markedly reduced with IGF-I treatment. IGF-I treatment resulted in a 3- to 5-fold increase in 38--44 kDa and 28--30 kDa IGF binding proteins, although in UN animals, there was an impaired and differential up-regulation of these insulin-like growth factor binding proteins following IGF-I treatment. The 24-kDa IGF binding protein representing IGF binding protein-4 was down-regulated in all IGF-I-treated animals, but the decrease was more marked in UN animals. Our data suggest that IGF-I treatment alleviates hyperphagia, obesity, hyperinsulinemia, hyperleptinemia, and hypertension in rats programmed to develop the metabolic syndrome X.
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PMID:IGF-I treatment reduces hyperphagia, obesity, and hypertension in metabolic disorders induced by fetal programming. 1151 75

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.
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PMID:Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values. 1155 Jan 5

Several trials have suggested that insulin-like growth factor-1 (IGF-1) may have a pathophysiological role in the development of arterial essential hypertension. To verify the possible association of IGF-1 with left ventricular morphological and functional echocardiographic parameters in hypertension, we studied 40 male patients with newly diagnosed hypertension and 15 normotensive control subjects. Doppler echocardiography was performed and circulating free IGF-1 levels were determined in all subjects. Circulating free IGF-1 levels were higher in hypertensives than in control subjects (P<0.01). A significant inverse correlation was observed between free IGF-1 and isovolumic relaxation time in the overall population (r=-0.37, P<0.01) and in hypertensives (r=-0.57, P<0.0001), whereas this relation disappears in normotensives. These results were confirmed by multivariate analysis. The present study confirms that arterial essential hypertension represents a clinical condition associated with an increased synthesis of IGF-1. The observation of an inverse, independent association between free IGF-1 and isovolumic relaxation time suggests 2 alternative hypotheses: a possible beneficial effect of IGF-1 to diastolic relaxation or a resistance to IGF-1 in hypertension.
Hypertension 2001 Oct
PMID:Inverse association between free insulin-like growth factor-1 and isovolumic relaxation in arterial systemic hypertension. 1164 Dec 96

To examine the role of insulin-like growth factor-1 (IGF-1) in renal atrophy of rats with two-kidney, one-clip (2K1C), in which the clipped kidney atrophies, and in the one-kidney, one-clip (IK1C) model of renovascular hypertension, in which it hypertrophies, we studied levels of IGF-I, mRNA, and protein in 2K1C, IK1C, and unilateral nephrectomy (NPX) in rats by solution-hybridization RNase protection, and radioimmunoassay, respectively, both cross-reactively and longitudinally at 3, 10, and 30 days after clipping. Three days after clipping, there were no differences in blood pressure or kidney size; however, 10 and 30 days postoperation, the clipped kidney shrank in the 2K1C model. The nonclipped 2K1C and the clipped lK1C and unilateral nephrectomy kidneys increased in weight (P < .05. At day 3 the IGF-I levels were lower (557 +/- 54, 335 +/- 61 ng/g in control and clipped 2K1C, P < .05, v 1,074 +/- 186, 1,109 +/- 54, and 1,154 +/- 200 ng/g kidney, nonclipped 2K1C, 1K1C, and NPX, respectively). At 30 days the IGF-I levels were 300 +/- 24 ng/g in control (P < .05) v clipped 2K1C, 160 +/- 19, 218 +/- 20 ng/g in nonclipped 2K1C and 406 +/- 33 and 470 +/- 34 ng/g in 1K1C and NPX, respectively (P < .05) v control and clipped 2K1C. Kidney mRNA was increased in the clipped 2K1C. In conclusion, the kidney that had higher IGF-I levels early in nonclipped 2K1C, 1K1C, and nephrectomy hypertrophied, and the kidney (clipped 2K1C) that failed to increase IGF-I atrophied. IGF-I levels are dissociated from the local mRNA message.
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PMID:Atrophy or hypertrophy in chronic renal ischemia: role of the IGF-I system. 1177 29

Risk factors for progression of kidney disease include hypertension, proteinuria, male sex, obesity, diabetes mellitus, hyperlipidemia, smoking, high-protein diets, phosphate retention, and metabolic acidosis. Angiotensin II production upregulates the expression of transforming growth factor-beta1, tumor necrosis factor-alpha, nuclear factor-kappaB, and several adhesion molecules and chemoattractants. In addition to angiotensin, other vasoactive compounds, such as thromboxane A(2), endothelin, and prostaglandins, are upregulated. Treatment with one of several growth factors may ameliorate the progression of kidney disease: insulin-like growth factor-1, hepatocyte growth factor, and bone morphogenetic protein-7.
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PMID:Progression of chronic renal disease. 1261 42

To test the hypothesis that the serum and glucocorticoid regulated kinase (SGK1) is of relevance to blood pressure in man, we recruited monozygotic (MZ) (126 pairs) and dizygotic (DZ) (70 pairs) normotensive twin subjects and parents of DZ twins. Blood pressure was measured in a controlled fashion recumbent, sitting, and upright. We documented genetic variance on blood pressure in all positions. We then relied on microsatellite markers at the SGK1 gene locus (D6S472, D6S 1038, and D6S270) and two single nucleotide polymorphisms within the SGK1 gene. We found significant linkage of the SGK1 gene locus to diastolic blood pressure (p<0.0002) and suggestive evidence for linkage for systolic blood pressure (p<0.04), documenting the locus as a QTL for blood pressure. We next performed association, using all DZ twins and an MZ member from each pair. We found significant associations between both SNP variants and blood pressure, as well as a significant interaction between the SNPs enhancing the effect. This combined effect of the polymorphisms was confirmed in an independent sample of 260 young normotensive men. These data, coupled with our earlier observations linking the insulin-like growth factor-1 gene locus to blood pressure lead us to conclude that the SGK1 gene is relevant to blood pressure regulation and probably to hypertension in man.
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PMID:Twin studies in the analysis of minor physiological differences between individuals. 1264 2

Vascular medial thickening, a hallmark of hypertension, is associated with vascular smooth muscle cell (VSMC) hypertrophy and hyperplasia. Although the precise mechanisms responsible are elusive, we have shown that strain induced regulation of autocrine insulin-like growth factor-1 (IGF-1) and nitric oxide (NO) reciprocally modulate VSMC proliferation. Therefore, we investigated potential IGF-1 and NO abnormalities in young (10-week-old) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and their respective VSMC ex vivo. The SHR had increased mean arterial pressure (173 +/- 2 v 128 +/- 3 mm Hg, n = 24, P <.05) but similar pulse pressures (31 +/- 2 v 30 +/- 3 mm Hg; P >.05) v WKY. The SHR exhibited increased aortic wall thickness in comparison with WKY (523 +/- 16 v 355 +/- 17 micro m; P <.05). No differences were seen in plasma combined NO(2) and NO(3) (NO(x)) (0.48 +/- 0.11 mmol/L for WKY v 0.58 +/- 0.18 mmol/L for SHR) or plasma IGF-1 (1007 +/- 28 ng/mL for WKY v 953 +/- 26 ng/mL for SHR). Aortic VSMC from SHR displayed enhanced proliferation in comparison with WKY (P <.05). Underlying this enhanced proliferation was altered SHR VSMC sensitivity to the antiproliferative NO donor 2,2"[Hydroxynitrosohydrazono] bis-ethanimine (DETA-NO) (ID(50): 270 +/- 20 mmol/L for SHR; 150 +/- 11 mmol/L for WKY; P <.05). Basal cyclic guanosine monophosphate (cGMP) secretion from SHR VSMC was 65-fold greater than that seen from WKY (P <.001). In response to DETA-NO, cGMP secretion from SHR VSMC increased modestly (1.5-fold; P <.01), whereas treatment of WKY VSMC resulted in a 26-fold (P <.001) increase in cGMP. The SHR VSMC did not respond to exogenous IGF-1, whereas WKY VSMC exhibited a dose dependent increase in proliferation with IGF-1 (10(-10) to 10(-7) mol/L). These data suggest that VSMC hyperplasia in early hypertension is not reflected by imbalances in plasma IGF-1 or NO. Rather, altered SHR VSMC sensitivity to NO is likely responsible in part for the observed hyperproliferation seen in early stages of hypertension.
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PMID:Altered insulin-like growth factor-1 and nitric oxide sensitivities in hypertension contribute to vascular hyperplasia. 1274 2


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