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)

Angiotensin II (Ang II) has growth-stimulatory properties on different renal cell types. However, possible growth effects of this vasoactive peptide on endothelial cells isolated from the glomerular microvasculature have not been formally investigated. Therefore, we isolated and characterized primary cultures of rat glomerular endothelial cells. We used a simple technique in which collagenase-treated glomeruli were sparsely plated in several 96-well culture plates and microscopically screened for cobblestone-like outgrowth. After two limiting dilutions, homogeneous cultures were obtained. Cells were characterized by positive staining for the endothelial markers factor VIII, CD 31, endothelial leukocyte adhesion molecule-1, and the lectin Bandeiraea simplificifolia. Ang II stimulated the synthesis and release of endothelin-1 in culture supernatants. Moreover, in contrast to syngeneic mesangial cells, glomerular endothelial cells expressed angiotensin-converting enzyme. Ang II stimulated a mild but significant proliferation of quiescent cells, as measured by [3H]thymidine incorporation and direct cell counting. This mitogenesis was transduced by losartan-blockade angiotensin type 1 receptors. Moreover, Ang II mediated phosphorylation of mitogen-activated protein kinase 2 and induction of transcripts for the immediate early gene Egr-1. Our results indicate that Ang II is a moderate mitogen for primary cultures of rat glomerular endothelial cells and activation of these metabolically active cells may play a role in the pathophysiology of several types of glomerulonephritis. Moreover, remodeling of glomerular endothelial cells by Ang II may be important in the progression of structural renal damage during the course of hypertensive injury.
Hypertension 1996 Apr
PMID:Angiotensin II is mitogenic for cultured rat glomerular endothelial cells. 861 66

To identify the sequence of events associated with the development of reduced vessel density (rarefaction) in hypertension, microvessel density and ultrastructure were assessed in the cremaster muscle of rats subjected to a 75% surgical reduction of renal mass and normotensive sham-operated control rats. Rats with reduced renal mass (RRM rats) and sham-operated rats were then maintained on either a high salt (4.0% NaCl) or a low salt (0.4% NaCl) diet for 3 days. Acute exposure to the high salt diet significantly increased mean arterial pressure in RRM rats but did not affect sham-operated control rats. Quantitative fluorescence microscopy of cremaster muscle whole mounts using rhodamine-labeled Griffonia simplicifolia I lectin revealed substantial rarefaction of microvessels in both RRM hypertensive rats and normotensive sham-operated rats on a high salt diet relative to corresponding control rats on a low salt diet. Confocal microscopy revealed a heterogeneous distribution of microvessels in RRM rats on a high salt diet, with some areas largely devoid of vessels. RRM and sham-operated rats on a high salt diet both exhibited changes in arteriolar ultrastructure, which included a loss of basement membranes and a dissociation of the endothelial and smooth muscle components of the vascular wall, resulting in a loss of vessel integrity. These observations demonstrate that a rapid loss of microvessels can occur not only in rats with RRM hypertension but also in normotensive rats on a high salt diet. This loss of microvessels results from structural alterations, which differ from the degenerative processes associated with microvascular rarefaction in rats with chronic RRM hypertension.
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PMID:Rapid microvessel rarefaction with elevated salt intake and reduced renal mass hypertension in rats. 875 11

In this study we hypothesized that reduced renal mass (RRM) hypertension, which is associated with a chronic reduction in vessel density, could reduce steady-state muscle performance. Vessel density and isometric tetanic force from the in situ gastrocnemius-plantaris-soleus muscle group were studied in age-matched normotensive sham-operated control (HSS) and hypertensive RRM rats on a high-salt (4.0% NaCl) diet (HSRRM) and a low-salt (0.4% NaCl) diet (LSS and LSRRM, respectively). The Achilles tendon was isolated and connected to a force transducer. Peak isometric tension elicited by sciatic nerve stimulation (1/s for 10 min, 50 impulses/s for 330 ms) was not different between the groups. In the LSS, HSS, and LSRRM groups, tension decreased similarly at 3 min to 375 +/- 22, 447 +/- 26, and 424 +/- 21 g/g, respectively. Tension was significantly reduced in the HSRRM group (203 +/- 45 g/g) relative to the LSS, HSS, and LSRRM groups by 3 min. These differences in steady-state tension persisted throughout the remainder of the experiment. Microvessel density, measured by the lectin fluorescence technique, was reduced significantly only in the soleus, plantaris, and medial gastrocnemius of the HSRRM rats. We conclude that RRM hypertension results in reductions in vessel density (rarefaction) that are associated with decreased steady-state muscle performance.
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PMID:Decreases in steady-state muscle performance and vessel density in reduced renal mass hypertensive rats. 877 43

The clinical, histologic, and immunohistochemical features of six cases of hemorrhagic adrenal pseudocysts are reported together, with a review of the English literature on this topic since 1950. The mean age at presentation was 57 years (range, 30-72 yr). There were four men and 2 women. The average cyst size was 9.2 cm (range, 6-16 cm). In four patients, the hemorrhagic adrenal pseudocysts were incidental findings. The remaining two patients presented with an abdominal mass and hypertension, respectively. The hemorrhagic pseudocysts were unilocular cystic masses surrounded by a fibrous capsule and containing abundant amorphous material, blood, and fibrin. Numerous dilated, thin-walled, vascular channels that stained strongly for Factor VIII-related antigen, collagen IV, laminin, Ulex europaeus agglutinin I lectin, and CD34 were present within the fibrous capsule, cyst contents, and surrounding residual adrenal gland. These findings support a vascular origin for these lesions, and they are thought, therefore, to be related to endothelial adrenal cysts. The literature review of 111 vascular adrenal cysts (85 hemorrhagic pseudocystic type and 26 endothelial type) showed similar clinical features. The mean age at presentation was 44.5 years (range, 5 d-95 yr), with a female predominance (62%). The most common clinical presentation was abdominal pain (35%), followed by incidental findings (32%). There were no significant clinical differences between hemorrhagic and endothelial type cysts. In some cases, the presence of intracystic islands of cortical cells can cause diagnostic confusion with adrenal cortical tumors. The presence, however, of a rich intracystic and capsular vascular network, normal-appearing islands of cortical cells, and abundant thrombotic fibrinous material, rather than necrotic tumor cells, should rule out the possibility of a degenerating adrenal cortical neoplasm.
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PMID:Vascular adrenal cysts: a clinicopathologic and immunohistochemical study of six cases and a review of the literature. 919 68

The periaqueductal gray matter (PAG) has been implicated in a variety of different functions, including autonomic regulation. Chemical stimulation of the lateral PAG produces hypertension and tachycardia while activation of the ventrolateral PAG produces the opposite effect. While these effects are the result of alterations in sympathetic activity, little is known about whether the PAG can modulate vagal functions as well. The anterograde axonal tracing method using the plant lectin Phaseolus vulgaris leucoagglutinin (PHA-L) was used to determine whether both of the lateral and ventrolateral PAG columns project to vagal preganglionic neurons and/or to the nucleus tractus solitarius (NTS). Highly restricted PHA-L injections were made in all four PAG columns throughout their rostrocaudal extent in rats. Labeled fibers were visualized by immunohistochemistry and studied in relationship with choline acetyltransferase (ChAT) immunostained parasympathetic preganglionic neurons of the dorsal motor vagal nucleus (DMV) and nucleus ambiguous (NA). The lateral PAG projects to the lateral DMV and to the caudal part of the external NA. The ventrolateral PAG innervates the same regions and also projects to the rostral part of the external NA -- a site that contains cardiac parasympathetic preganglionic neurons. Both the lateral and ventrolateral PAG project to the NTS in a similar fashion innervating the medial, ventrolateral and commissural subnuclei. In summary, the lateral and ventrolateral PAG have similar patterns of innervation of the NTS and DMV, but their projection to the NA is different: the rostral external NA receives innervation only from the ventrolateral PAG and the lateral PAG innervates the caudal part.
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PMID:Periaqueductal gray matter projection to vagal preganglionic neurons and the nucleus tractus solitarius. 929 20

We report the identification of a unique repetitive sequence in the rat endothelial receptor for oxidized low-density lipoprotein (LOX-1) and unexpected blood-pressure-associated regulation of its expression, a new link between lipid metabolism and blood-pressure control. A rat aorta cDNA library was constructed and screened with a probe synthesized by degenerate PCR. Rat LOX-1 cDNA encoded a protein of 364 amino acids that showed approximately 60% similarity to its bovine and human counterparts. The protein consisted of intracellular N-terminal, transmembrane and extracellular lectin-like domains. Rat LOX-1 was unique in having three repeats of a 46-amino-acid motif between the transmembrane and lectin-like regions. Two isoforms of mRNA were found to be generated by alternative use of two polyadenylation signals in a tissue-specific manner. The 3'-untranslated region contained multiple A+U-rich elements for rapid degradation of mRNA. Northern-blot analysis revealed that LOX-1 mRNA was expressed predominantly in the lung. Quite unexpectedly, the expression was dramatically up-regulated in the aorta in hypertensive SHR-SP/Izm rats compared with very low levels in control WKY/Izm rats, suggesting a potential role for LOX-1 in the pathogenesis of hypertension as well as atherosclerosis.
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PMID:Unique repetitive sequence and unexpected regulation of expression of rat endothelial receptor for oxidized low-density lipoprotein (LOX-1). 949 15

Epidemiologic studies reveal that women have a significantly lower age-adjusted morbidity and mortality from cardiovascular disease than men, suggesting that gender is a cardiovascular disease risk factor. The mechanism of the "gender protection" is unknown. In this study, we investigated the microvascular remodeling in reduced renal mass plus a high salt (4.0% NaCl) diet model of hypertension (RRM + HS). We hypothesized that women would be protected from the increase in blood pressure and from the microvascular rarefaction associated with RRM + HS hypertension. Studies were designed to determine whether female rats were less susceptible to changes in microvessel density during RRM + HS. Microvessel density was measured in male and female low salt (0.4% LS) sham-operated controls (Sham + LS) and after 3 days or 4 weeks of RRM + HS hypertension. The microcirculation of hind limb (medial and lateral gastrocnemius, plantaris, soleus) muscles was visualized using rhodamine-labeled Griffonia simplicifolia I lectin. Tissue sections were examined by videomicroscopy and microvessel density was determined by quantitative stereology. As shown previously, mean arterial pressure increased to 160 +/- 8 mm Hg and microvessel density decreased (>30% decrease in all beds) in male RRM + HS. In contrast, mean arterial pressure of female RRM + HS rats was modestly increased from 101 +/- 2 to 118 +/- 4 mm Hg. Despite previous results showing a reduction in microvessel density of both normotensive and hypertensive male rats on a high salt diet, microvessel density of female RRM + HS rats was not reduced at either time. These results suggest that gender protection in the RRM rat extends beyond an attenuation of the increase in pressure to an immunity from microvascular rarefaction.
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PMID:Gender-specific protection from microvessel rarefaction in female hypertensive rats. 971 94

Previous studies in rats have shown that blockade of bradykinin B2 receptors (B2R) in combination with a high-salt intake during gestation result in poor postnatal survival and long-term hypertension in the offspring. In this study, we examined the fetal ontogeny of B2R and determined the consequences of gestational B2R blockade and high salt on kidney development. B2R gene expression is induced on embryonic day (E16) of fetal metanephrogenesis and remains sustained until term. The earliest expression of the B2R protein is observed on apical membranes of ureteric bud branches and in capillary loop stage glomeruli. By the end of gestation, B2R becomes restricted to more-differentiated tubules in the deep cortex and medulla. Pairs of rats on normal (0.12 mmol/g) or high (0.84 mmol/g) salt diets were mated at 14 weeks of age. The B2R antagonist, Icatibant (previously known as Hoe-140) (300 nmol/kg per day) or saline (vehicle) was infused intraperitoneally during gestation via osmotic minipumps. Fetuses were examined on E20 (n=27-36 per group). No significant differences in litter size or body weight were observed among the groups. Combined high-salt and Icatibant treatment caused aberrant fetal renal development characterized by tubular dysgenesis, widened stromal mesenchyme, and glomerular cysts. The dysgenetic tubules stained positively for the distal nephron lectin, Dolichos biflorus, and exhibited enhanced Bax expression and apoptosis. Renal microvascular development, the number of mature glomeruli, and percentage of proliferating glomerular cells were not affected. Gestational Icatibant or high salt alone had no deleterious effects on fetal nephrogenesis. We conclude that gestational blockade of the kallikrein-kinin system impairs fetal nephrogenesis if combined with an intrauterine stressor such as high-salt intake. B2R may play a protective role during segmental nephron differentiation.
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PMID:Fetal ontogeny and role of metanephric bradykinin B2 receptors. 1077 71

This study examines the clinical features, pathologic findings, and outcome of 24 patients with biopsy-proven lithium toxicity. The patient population was 50% male, 87.5% Caucasian, and had a mean age of 42.5 yr (range, 26 to 57). Mean duration of lithium therapy for bipolar disorder was 13.6 yr (range, 2 to 25). All patients were biopsied for renal insufficiency (mean serum creatinine 2.8 mg/dl; range, 1.3 to 8.0), with associated proteinuria >1.0 g/d in 41.7%. Nephrotic proteinuria (>3.0 g/d) was present in 25%. Other features included nephrogenic diabetes insipidus in 87% and hypertension in 33.3%. Renal biopsy revealed a chronic tubulointerstitial nephropathy in 100%, with associated cortical and medullary tubular cysts (62.5%) or dilatation (33.3%). All of the renal cysts stained for epithelial membrane antigen, while 51.4% stained with lectin Arachis hypogaea, and only 3.8% stained with Tetragonolobus purpureas, indicating they originated from distal and collecting tubules. The degree of tubular atrophy and interstitial fibrosis was graded as severe in 58.3%, moderate in 37.5%, and mild in 4.2% of cases. There was a surprisingly high prevalence of focal segmental glomerulosclerosis (50%) and global glomerulosclerosis (100%), sometimes of equivalent severity to the chronic tubulointerstitial disease. The significant degree of foot process effacement (mean 34%, five of 14 cases with >50%) suggests a potential direct glomerular toxicity. Focal segmental glomerulosclerosis correlated with proteinuria >1.0 g/d (P = 0.0014, Fisher exact test). Despite discontinuation of lithium, seven of nine patients with initial serum creatinine values >2.5 mg/dl progressed to end-stage renal disease (ESRD). Only three patients, all with initial serum creatinine <2.1 mg/dl, had subsequent improvement in renal function. By Kaplan-Meier survival analysis, the only significant predictor of progression to ESRD was serum creatinine >2.5 mg/dl at biopsy (P = 0. 008). In conclusion, lithium nephrotoxicity primarily targets distal and collecting tubules, with a higher incidence of proteinuria and associated glomerular pathology than recognized previously. Renal dysfunction is often irreversible despite lithium withdrawal, and early detection is essential to prevent progression to ESRD.
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PMID:Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. 1090 57

Oxidatively modified low-density lipoprotein (ox-LDL) leads to endothelial activation, dysfunction and injury. Recently, a novel lectin-like receptor for ox-LDL (LOX-1) has been identified, primarily in the endothelial cells, and it allows uptake of ox-LDL into endothelial cells. This receptor is transcriptionally upregulated by tumor necrosis factor-alpha, angiotensin II, shear stress and ox-LDL itself. The expression of this receptor activates a variety of intracellular processes that lead to expression of adhesion molecules and endothelial activation. This receptor is highly expressed in the blood vessels of animals and humans with hypertension, diabetes mellitus and atherosclerosis. Expression of this receptor may also be relevant in intra-arterial thrombogenesis and myocardial ischemia-reperfusion injury. Identification and regulation of this receptor and understanding of signal transduction pathways may lead to new therapies of diseases characterized by endothelial dysfunction.
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PMID:Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor. 1198 3


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