UMLS:C0020538 - FACTA Search

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)

CRF is unusual in that it is synthesized and released from the placenta into the circulation in humans, reaching levels in the third trimester that would normally be expected in the hypothalamic portal system during stress. This rise is even more pronounced in pregnancy-induced hypertension and preterm labour. Paradoxically, there is no associated rise of either ACTH or cortisol. This lack of biological response and the stability of the peptide in human (but not rat) plasma in vitro initiated a search for the human CRF-binding plasma protein. This CRF-BP proved to have a molecular mass in the region of 40 kDa, and has been purified to homogeneity. It has an affinity constant in the nanomolar range and when mixed with appropriate amounts of CRF completely inhibits the ACTH-releasing activity of the peptide in vitro. With the cloning of the cDNA for CRF-BP, sufficient pure material has become available for the development of a radioimmunoassay. Although CRF-BP levels in pregnant women are normal in the second trimester, they begin to fall by week 35, reaching approximately 50% of normal values by term. The net effect of this would be an accelerated increase in free, potentially biologically active CRF.
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PMID:Corticotropin-releasing factor and its binding protein in human plasma. 838 5

1. We investigated the central role of corticotrophin-releasing factor (CRF-41) in psychological stress-induced responses, including cardiovascular, thermoregulatory and locomotive activity in free-moving rats. 2. Psychological stress was induced by cage-switch stress. After rats were placed in the novel environment, blood pressure, heart rate, body temperature and locomotive activity significantly increased. The intracerebroventricular (I.C.V.) injection of alpha-helical CRF(9-41), a CRF-41 receptor antagonist, significantly attenuated the stress-induced hypertension, tachycardia, hyperthermia and increase in locomotive activity. However, in unstressed rats, the I.C.V. injection of alpha-helical CRF(9-41) had no effect on physiological parameters measured in this study. 3. In unstressed rats, the I.C.V. injection of CRF-41 (1 microgram and 10 micrograms) increased blood pressure, heart rate, body temperature and locomotive activity in a dose-dependent manner. The changes in these responses were quite similar to those observed during cage-switch stress. 4. The results suggest that central CRF-41 plays an important role in psychological stress-induced hypertension, hyperthermia, tachycardia and increase in locomotive activity. However, it is likely that central CRF-41 does not contribute to normal cardiovascular and body temperature regulation when rats are free from stress.
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PMID:The central role of corticotrophin-releasing factor (CRF-41) in psychological stress in rats. 848 93

Corticotropin-releasing factor-binding protein (CRF-BP) is suggested to play a role in modulating the activity of the hypothalamus-pituitary-adrenal axis during pregnancy, counteracting the actions of circulating or locally acting CRF. The aim of the present study was to evaluate whether maternal levels of CRF-BP and CRF are modified in pregnant women with a high risk of developing pregnancy-induced hypertension (n = 21). A group of nine patients developed the disease between 25-35 weeks gestation, and sequential blood samples were taken every 5 weeks throughout the pregnancy. As a control group, healthy pregnant women were studied (n = 9) using the same protocol; a group of women with pregnancy-induced hypertension (n = 5) was studied starting from the time of diagnosis. In a subgroup of patients (n = 10), CRF-BP and CRF levels were studied after 5 weeks of antihypertensive treatment. Levels of CRF-BP were determined using a specific RIA, whereas CRF was evaluated by a two-site immunoradiometric assay. In patients at risk, circulating levels of CRF-BP followed the same pattern as that in healthy controls, showing a significant decrease at term (36-40 weeks; P < 0.05). A significant and progressive increase in plasma CRF levels was observed in both groups of pregnant women; the highest values were found at term (P < 0.01). In the nine patients who developed pregnancy-induced hypertension, maternal levels of CRF-BP at the onset of signs and symptoms were lower than control values, and CRF levels were significantly higher at the onset of the disease (P < 0.01). Similarly, in these hypertensive patients studied at the time of hospitalization, CRF-BP levels were lower whereas those of CRF were higher than levels in healthy patients (P < 0.01). No effect of antihypertensive therapy on either CRF-BP or CRF levels was observed. The present study shows an inverse correlation between reduced plasma CRF-BP levels and increased CRF levels in the maternal circulation of patients with pregnancy-induced hypertension, and indicates that these hormonal changes do not occur before the onset of disease, suggesting that the measurement of these polypeptides in maternal plasma does not predict the development of hypertension.
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PMID:High levels of corticotropin-releasing factor (CRF) are inversely correlated with low levels of maternal CRF-binding protein in pregnant women with pregnancy-induced hypertension. 863 16

The cardiac abnormalities that complicate chronic renal failure and renal replacement therapy are not well characterized in young people. These abnormalities are becoming more important because successful renal transplantation has resulted in children with end-stage renal failure living longer. Echocardiographic abnormalities of cardiac function and structure were studied in children and young adults (< 27 years old) with chronic renal failure (CRF, N = 32), end-stage renal failure treated with chronic peritoneal dialysis (CPD, N = 10) or renal transplantation (N = 30) or controls (N = 60). Left ventricular mass indexed for height (LVM/Ht and LVM/Ht2.7) and body surface area (LVM/SA), fractional shortening, measurement of left ventricular diastolic function (peak E and A wave velocities and the EA ratio) and structural (such as valvular) abnormalities were determined by echocardiography. The median (and range) of LVM/Ht in the groups were control 51.8 (23.1 to 119.8), CRF 60.2 (22.2 to 135.8), CPD 80.2 (14.5 to 100.9) and transplant group 97.8 (51.2 to 182.1) g/m. The increases in LVM/Ht, LVM/Ht2.7 and LVM/SA in the transplant group were significant (P < 0.01). The CRF group had significantly increased LVM/Ht2.7 and LVM/SA (P < 0.01). Systolic function was not significantly different between the groups. A significant correlation between creatinine and LVM indexed for height was found in the CRF group. Systolic or diastolic blood pressure could not be correlated with LVM indices in the transplant group. Changes in diastolic function were found (increased peak A wave velocity and decreased E/A ratios in the CRF and CPD groups, and increased peak E wave velocity in the transplant group). The study demonstrated that left ventricular hypertrophy is a frequent and often severe finding in children with chronic renal failure and those treated with renal replacement therapy. Factors other than hypertension and anaemia are important, and evidence was found for a link between serum creatinine and increased left ventricular mass prior to end-stage renal failure.
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PMID:Left ventricular abnormalities in children, adolescents and young adults with renal disease. 887 76

Hypertension in 5/6 nephrectomized (CRF) rats is partly related to increased activity of the sympathetic nervous system. We have previously shown a greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for hypertension in CRF rats. To further evaluate the role of renal afferent nerves in the regulation of blood pressure, and whether renal afferent pathways integrate with the posterior hypothalamus, we studied the effects of an intrarenal injection of 50 microliters of 10% phenol on blood pressure and NE secretion from the posterior hypothalamus of Sprague-Dawley rats. Mean arterial pressure increased from 89 +/- 4.0 to 114 +/- 4.3 mm Hg in rats which received intrarenal injection of phenol, but it did not change in rats that received vehicle (95 +/- 4.3 and 89 +/- 3.6 mm Hg, respectively). Renal denervation totally prevented the increase in blood pressure caused by intrarenal injection of phenol. The secretion of NE from the posterior hypothalamus increased from 139 +/- 4.8 to 250 +/- 9.9 pg/ml (P < 0.01) in rats that received intrarenal phenol, but it did not change in rats which received vehicle or in those with renal denervation. In CRF rats NE secretion from the posterior hypothalamus was greater than in control and CRF rats subjected to dorsal rhizotomy. These studies show that afferent impulses from an injured kidney increase NE secretion from the posterior hypothalamus and raise blood pressure. NE secretion is higher in the posterior hypothalamus of CRF than control rats. The posterior hypothalamus appears to be an important integrative structure of the sympathetic regulation of blood pressure.
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PMID:Renal afferent impulses, the posterior hypothalamus, and hypertension in rats with chronic renal failure. 906 4

We have reported that uremic plasma filtrates (UF) inhibit the red blood cell (RBC) membrane calcium pump. The inhibitor was dialyzable, smaller than 3,000 molecular weight, heat-stable, and protease-resistant. In the present study, we used reverse-phase preparative HPLC, analytical HPLC, and Sephadex G-25 elution to identify inhibitory fractions. Inhibition was confirmed in three different bioassays: (1) Sr2+ efflux in intact RBC, the primary bio-assay; (2) 45Ca efflux in intact RBC; and (3) calcium ATPase activity in isolated RBC membranes. Active fractions were analyzed by mass spectrometry, capillary electrophoresis, enzymatic analysis, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. These demonstrated a number of compounds, including: sugars, polyols, osmolytes like betaine and myoinositol, amino acids, and other metabolites, such as 3-D-hydroxybutyrate, dimethylglycine, trimethylamine-N-oxide, guanidinoacetic acid and glycine. Many individual compounds were then tested for an effect on the calcium pump. Thus, HPLC was able to separate a substantial number of compounds in inhibitory fractions. Efforts are under way for precise identification of the inhibitor, to advance our understanding of uremic toxicity and/or hypertension in CRF.
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PMID:HPLC fractions of human uremic plasma inhibit the RBC membrane calcium pump. 908 69

The association between hypertension and chronic renal disease is well recognized. Various factors may play a role in the pathogenesis of hypertension in chronic renal failure. Those include sodium retention and volume expansion, and increased activity of vasoconstrictors, such as the renin-angiotensin system. More recently, increased activity of the sympathetic nervous system has emerged as a leading factor in the pathogenesis of hypertension in these patients. We have used the model of 5/6 nephrectomized rats to study the role of the sympathetic nervous system in the pathogenesis of this form of hypertension. We have shown greater norepinephrine turnover rate in the posterior hypothalamic nuclei and locus coeruleus of CRF than control rats. Dorsal rhizotomy prevented the rise in blood pressure and the increase in NE turnover rate in the posterior hypothalamus and the locus coeruleus. An acute injury to the kidney produced by intrarenal injection of phenol, causes an immediate rise in blood pressure and in NE secretion from the posterior hypothalamus, that can be prevented by renal denervation. Dorsal rhizotomy prevented the development of hypertension in rats with chronic renal failure. The studies suggest that afferent impulses from the kidney to central integrative structures in the brain may be responsible for the rise in blood pressure in chronic renal failure.
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PMID:Neurogenic factors and hypertension in chronic renal failure. 937 24

M-mode, two-dimensional, and Doppler echocardiography were performed in 38 chronic renal failure (CRD) patients on conservative management, 35 patients on hemodialysis, and 36 matched controls. The controls were matched for age, sex, and comorbidities. The incidence of hypertension, left ventricular (LV) end diastolic volume, LV end systolic volume, and LV mass index were significantly higher in patients on hemodialysis compared to the controls. The LV parameters in the predialysis patients were not significantly different from the controls, except the LV end systolic internal dimensions were significantly higher in the CRF patients. Multiple regression analysis underscored the strong association between increase in LV mass index (LVMI) and hypertension. The diabetic patients with renal failure had large LV internal diameter and end diastolic volume compared to non-diabetics. Systolic function was well preserved even in hypertensive and diabetic patients with uremia. The incidence of diastolic dysfunction and asymmetrical septal hypertrophy were not significantly different in the three groups of patients.
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PMID:Left ventricular morphology in chronic renal failure by echocardiography. 941 37

1. Arginine vasopressin (AVP) is synthesized in specific brain regions including the magnocellular and parvocellular divisions of the paraventricular nucleus (PVN). Whereas magnocellular AVP responds to osmotic stimuli and functions mainly--although not exclusively--as an antidiuretic hormone, that produced in the parvocellular region controls the hypothalamus-pituitary-adrenal (HPA) axis, in conjunction with CRF. 2. In view of the reported sex differences in control of the HPA axis, we studied if these also pertain to AVP mRNA in the PVN of ovariectomized-estrogenized female rats and male rats determined by in situ hybridization. AVP mRNA was measured in intact rats, adrenalectomized (ADX) rats and ADX receiving dexamethasone (DEX) of both sexes. 3. Computerized autoradiography showed that in both sexes, AVP mRNA levels in the parvocellular division of the PVN increased after adrenalectomy and decreased following DEX. However, the reduction by DEX was more pronounced in female rats. No changes were found for the magnocellular region. Grain counting analysis of the medial-medial (MMP) and medial-lateral (MLP) subdivisions of the parvocellular region showed that the average number of grains per cell area in the MMP region of adrenally intact female rats was higher than that in males. However, in females there was no clear-cut effect of adrenalectomy on AVP mRNA levels, although the reduction after DEX treatment was again greater than that in male rats. Frequency histograms constructed by plotting the number of cells vs the number of grains per area substantiated the enhanced glucocorticoid negative control of AVP mRNA in the MMP and MLP of female rats. 4. The results indicated a sexual dimorphism in the glucocorticoid-dependent plasticity of AVP mRNA levels in the PVN. Because AVP mRNA expression differs between sexes under basal levels, after adrenalectomy, and after DEX treatment, these plastic changes may differentially condition the response to stress. Taking into consideration that stress and AVP may play a role in neurogenic hypertension, the possibility of sexual dimorphisms in AVP control may be important to assess the role of sex hormones in stress and steroid-derived hypertension.
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PMID:Sex difference in glucocorticoid regulation of vasopressin mRNA in the paraventricular hypothalamic nucleus. 944 52

Heightened hypothalamic-pituitary-adrenal (HPA) axis responses have been implicated in hypertension in the spontaneously hypertensive rat (SHR), but the exact mechanisms involved are poorly understood. To determine changes in gene expression in SHR in the paraventricular nucleus (PVN), stress-induced accumulation of CRF, CRF type 1 receptor (CRFR-1) genes, and immediate-early genes were examined using in situ hybridization in young (5 weeks old) and adult (12 weeks old) stroke-prone SHR (SHRSP), compared with normotensive Wistar Kyoto (WKY) rats. Restraint stress-induced accumulation of c-fos, jun B, and NGFI-B mRNA, and CRF hnRNA in the PVN was significantly higher in young and adult SHRSP than in WKY rats at 30 min, except for c-fos in young rats. CRFR-1 mRNA expression in the PVN was also significantly higher in adult SHRSP than in WKY rats at 120 min after stress onset. CRF mRNA was increased in response to stress in young SHRSP. The basal CRF mRNA level in the PVN was significantly lower in adult SHRSP than in WKY rats. Young SHRSP exhibit greater ACTH responses to stress without significant changes in plasma corticosterone concentrations. The adult SHRSP exhibited lower baseline concentrations of corticosterone and similar corticosterone response to stress with enhanced secretion of ACTH. Overall, these results demonstrated that stress-induced activation of immediate early genes and CRF gene transcription in the PVN, and ACTH secretion is enhanced in early hypertensive, young, and adult SHRSP, suggesting that they are probably not the result of chronic alterations in blood pressure. The abnormal hypothalamic-pituitary response to stress thus appears to be related to the development of hypertension.
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PMID:Stress-induced changes of gene expression in the paraventricular nucleus are enhanced in spontaneously hypertensive rats. 972 16

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