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

Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation.
Hypertension 1992 Jun
PMID:Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene. 159 69

Fibronectin expression was shown recently to increase in the rat aorta in response to experimental hypertension. Fibronectin is known to alter the phenotype of vascular smooth muscle and endothelial cells, and relative changes in the expression of different isoforms of fibronectin, generated by alternative splicing and distinguished by the absence or presence of inserts designated as EIIIA, EIIIB, and V, may reflect a change in cell phenotype. In the present study we examined the expression of alternatively spliced forms of aortic fibronectin during deoxycorticosterone-salt hypertension. Aortic RNA was analyzed quantitatively using Northern blot analysis and ribonuclease protection assays. Using Northern blot analysis, deoxycorticosterone-salt treatment for 21 days led to a 4.9-fold increase in EIIIA fibronectin messenger RNA, while EIIIB and V forms increased by 2.6- and 2.5-fold, respectively. As determined by ribonuclease protection assays, the percentage of fibronectin transcripts containing either EIIIA, EIIIB, or V in control aorta was 7.3%, 19%, and 40%, respectively. The percentage of EIIIA transcripts increased 42% over control levels after 21 days of deoxycorticosterone-salt treatment, whereas no proportionate change in the other alternatively spliced forms was found. Thus, all forms increased, but a selective increase in the EIIIA form was induced. Analogous increases in each of the fibronectin isoforms were found in the spontaneously hypertensive rats when compared with age-matched Wistar-Kyoto or Wistar rats, and 40-week-old animals showed increases over 10-week-old animals in all strains, consistent with an age-dependent increase in aortic fibronectin expression.
Hypertension 1992 Jul
PMID:Hypertension induces alternatively spliced forms of fibronectin in rat aorta. 161 48

Insulin-like growth factor I (IGF I), a potent growth factor in vitro, is present in blood and in multiple tissues and is a major mediator of the effects of growth hormone on postnatal growth. IGF I is internalized and retained largely intact in cultured vascular endothelial cells. Neovasculature transiently expresses IGF I immunoreactivity, but it is not known whether this represents internalization of the circulating growth factor or vascular cell synthesis of IGF I. As an initial approach to defining the role of endogenous production of IGF I in the growth program of the vessel wall, Northern hybridizations were performed with RNA from cultured rat aortic smooth muscle cells and bovine aortic endothelial cells. Rat aortic smooth muscle cells expressed three primary IGF I messenger RNA transcripts sized 8.2, 1.7, and 0.9-1.2 kb. Bovine aortic endothelial cells expressed one major and one minor IGF I transcript of 2.1 and 1.6 kb, respectively. IGF I gene expression in smooth muscle cells was also demonstrated by ribonuclease protection assays using a rat exon 3 riboprobe. Both endothelial and vascular smooth muscle cells secreted IGF I, as detected by radioimmunoassay of conditioned medium after separation of IGF I from its binding proteins by gel filtration chromatography. Because IGF I stimulates growth of vascular cells, characterization of IGF I gene expression in blood vessels may be key to understanding developmental as well as abnormal growth in the cardiovascular system.
Hypertension 1991 May
PMID:Insulin-like growth factor I gene expression in vascular cells. 170 44

In the kidney, 11 beta-dehydrogenase (11 beta-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11 beta-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid. Observations from these clinical studies indicate that 11 beta-DH conveys specificity for the mineralocorticoid receptor in distal tubules and collecting ducts. However, while some studies do indicate 11 beta-DH activity in rat distal tubules and collecting ducts, immunohistochemical studies localize 11 beta-DH only to proximal tubules. to resolve this dilemma, we have performed in situ hybridization localization of 11 beta-DH mRNA in rat kidney tissue using 35S-labeled sense and antisense cRNA probes to rat 11 beta-DH. In contrast to our immunohistochemical studies in which 11 beta-DH protein was localized predominantly to proximal tubules in the inner cortex, 11 beta-DH mRNA was expressed in tubules in both the inner and outer cortex, most probably proximal and distal tubules, and in collecting ducts extending across the corticomedullary junction to the papillary tip. Weak hybridization was also seen in glomeruli, but no hybridization to the sense 11 beta-DH cRNA or to sections pretreated with RNase-A was observed. We conclude that renal 11 beta-DH is suitably located to prevent access of glucocorticoid to the MR in an autocrine and not a paracrine fashion. 11 beta-DH in proximal tubules may protect the glucocorticoid receptor.
 ...
PMID:Localization of renal 11 beta-dehydrogenase by in situ hybridization: autocrine not paracrine protector of the mineralocorticoid receptor. 184 10

1. Using a ribonuclease-protection assay, renin mRNA levels were compared in the kidneys, livers, brains, hearts and adrenal glands of two-kidney, one-clip Goldblatt hypertensive rats with those of age-matched control rats at 4 weeks ('early') and 20 weeks ('chronic') after clipping, and in the kidneys and adrenal glands of rats treated for 3 weeks with deoxycorticosterone and salt (deoxycorticosterone-salt hypertension) with those of control rats. 2. While marked changes were observed in kidney renin mRNA levels in all three experimental groups compared with their respective controls, in most of the extra-renal tissue studied minimal, if any, difference was seen in renin mRNA levels between the hypertensive and control rats. 3. The findings suggest that in these extra-renal tissues renin gene expression is differently regulated from that in the kidney, and particularly that it is not profoundly affected by changes in the level of circulating angiotensin II. 4. An increase in renin mRNA was observed in the adrenal glands of the 'chronic' Goldblatt rats, which may be of relevance to the maintenance of hypertension in this model.
 ...
PMID:Renal and extra-renal levels of renin mRNA in experimental hypertension. 185 Oct 70

This case was a 51-year-old woman, who had been diagnosed as having rheumatoid arthritis at some clinic and had been treated with both non-steroidal anti-inflammatory drugs and steroid 3 years before visiting our clinic. When she noticed a decrease in visual acuity and general fatigue in June 1985, she was referred to an ophthalmologist of our hospital, and found to have blood pressure of 240/150 mmHg and KW grade IV retinal findings. She was admitted in our department to examine and treat malignant hypertension. On admission, remarkable hypergammaglobulinemia (29.3%), arthralgia, arthral deformity and pericardial effusion were present thus, she was suspected to be suffering from malignant rheumatoid arthritis. Anti-nuclear antibody (64X), anti-nuclear ribonucleoprotein antibody (64X) and anti-RNase sensitive antibody of anti-extractable nuclear antigens (ENA) antibody (81920X) were positive, while anti-RNase resistant antibody of anti-ENA antibody was negative. Immunologically, her condition was consistent with mixed connective tissue disease (MCTD). Since urinary protein was positive and creatinine clearance was 46.0 ml/min, renal function was thought to be diminished. Her chest roentgenogram revealed cardiomegaly (CTR 67.5%) and an increase in pulmonary vascular shadow. An echocardiogram demonstrated the presence of pericardial effusion. Plasma renin activity was 3.3 ng/ml/h and it was suspected that an intrarenal ischemic change resulted in increased renin release from the juxta-glomerular apparatus, leading to the marked hypertension. Treatment was started with prednisolone 60 mg/day during 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[A case of mixed connective tissue disease complicated with malignant hypertension]. 219 30

There is evidence that increased excretion of urinary enzymes and low-molecular mass proteins indicate impaired tubular function. The excretion of N-acetyl-beta-D-glucosaminidase (NAG), lysozyme, and ribonuclease in Type I diabetic patients with (n = 19) and without (n = 17) persistent proteinuria (urinary protein excretion greater than 0.5 g/day) was investigated and compared with this excretion in 30 weight- and gender-matched nondiabetic subjects without renal disease. Urinary NAG excretion was significantly higher in diabetic patients with and without persistent proteinuria (1.16 +/- 0.09 and 3.19 +/- 1.2 Umol/L creatinine, respectively) compared to controls (0.37 +/- 0.03 Umol/L creatinine p less than 0.01). In addition, the urinary excretion of lysozyme and ribonuclease was significantly increased in diabetic patients. Urinary NAG was found to correlate positively with albuminuria and proteinuria (r = 0.95 and 0.93, respectively), as well as with ribonuclease and lysozyme (r = 0.93 and 0.60; p less than 0.01) in patients with persistent proteinuria. Furthermore, NAG excretion was significantly related to the duration of diabetes (r = 0.36; p less than 0.05). No relationship existed between urinary NAG and serum creatinine, beta-2-microglobulin, and degree of metabolic control (HbA7). The lysozyme excretion, but not NAG excretion, was significantly related to hypertension in patients with clinical proteinuria. In conclusion, our results suggest a relationship between the development of tubular dysfunction and the impairment of glomerular function in diabetic nephropathy. An increased excretion of NAG and low-molecular mass proteins may indicate early nephropathy
 ...
PMID:Further evidence for tubular dysfunction in insulin dependent diabetes. 252 61

1. Renin messenger RNA (mRNA) levels were compared in the kidneys, livers, brains, adrenals, aortae and hearts of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 5 and 12 weeks of age using a ribonuclease-protection technique. 2. Relative levels of renin mRNA were increased in the kidney, liver, brain, adrenal and heart of the young SHR compared with the WKY. In the aorta, levels were similar in the two strains at 5 weeks. 3. In 12-week-old animals, while increased levels persisted in the liver, brain and adrenal of the SHR, the level in the kidney was now the same in the two strains and the levels in the heart and aorta were lower in the SHR compared with the WKY. 4. Renin mRNA levels in the kidneys of SHR and WKY were also compared by Northern blotting and confirmed the observations made with the ribonuclease-protection technique. 5. The findings indicate a widespread abnormality of renin gene expression in the SHR which is modulated in some tissues by the development of hypertension. 6. While the mechanism(s) for the abnormality remains to be determined, the increased renin mRNA levels in the SHR in several tissues concerned with blood pressure regulation suggests an important role for the renin-angiotensin system in the development and maintenance of hypertension. 7. However, the finding of increased renin mRNA in the liver also suggests abnormalities in other, as yet unknown, functions of the renin-angiotensin system in the SHR.
 ...
PMID:A widespread abnormality of renin gene expression in the spontaneously hypertensive rat: modulation in some tissues with the development of hypertension. 269 Nov 75

The effects of zinc supplementation on levels of various blood constituents and the outcome of pregnancy in 213 Hispanic women attending a prenatal clinic in Los Angeles was assessed in this double-blind study. The women were randomized into either a control (C) or a zinc-supplemented (Z) group and received similar vitamin and mineral supplements except that 20 mg zinc was added to the Z group's capsules. At the final interview, women (C + Z) with low serum Zn levels (less than or equal to 53 micrograms/dl) had higher (p less than 0.01) mean ribonuclease activity and lower (p less than 0.01) mean delta-aminolevulinic acid dehydratase activity than women with acceptable serum zinc levels. The incidence of pregnancy-induced hypertension was higher (p less than 0.003) in the C than in the Z group, but pregnancy-induced hypertension was not associated with low serum zinc levels at either the initial or final interview. The expected increase in serum copper levels was greater (less than 0.001) in women with pregnancy-induced hypertension (C + Z) than in normotensives. Except for pregnancy-induced hypertension, there was a higher incidence of abnormal outcomes of pregnancy in the noncompliers than in the compliers (C + Z).
 ...
PMID:Zinc supplementation during pregnancy: effects on selected blood constituents and on progress and outcome of pregnancy in low-income women of Mexican descent. 647 22

A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1-mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1-mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.
Hypertension 1995 Dec
PMID:Endothelin in the kidney in malignant phase hypertension. 749 Jan 50


1 2 3 4 5 6 Next >>