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)

Cardiac beta-adrenoceptors were studied in membrane fractions from spontaneously hypertensive rats (SHR) and rats with two-kidney, one clip hypertension (2K, 1C HT), using radioligand binding method. beta-Adrenoceptor concentration measured by [3H]-dihydroalprenolol (DHA) binding was significantly lower in cardiac membranes from two months old SHR than those from Wistar-Kyoto rats (WKY) (38.2 +/- 2.6 vs 45.1 +/- 1.8 fmol/mg protein, means +/- SEM, p less than 0.05). Cardiac membranes from 2K, 1C HT rats had also a lower concentration of beta-adrenoceptors than those from the sham-operated control rats at a week after operation (30.9 +/- 2.2 vs 47.8 +/- 1.6 fmol/mg protein, p less than 0.01). But receptor affinity remained unchanged. These reduced concentrations of beta-adrenoceptors were restored to control levels at 12 months old in SHR and at 6 weeks after operation in 2K, 1C HT rats, although age-dependent decrease in beta-adrenoceptor was observed. The decrease in beta-adrenoceptor was associated with increase in plasma noradrenaline levels during the earlier stages of hypertension. But there is no correlation between beta-adrenoceptor concentrations and plasma noradrenaline levels in the chronic stages of hypertension. No significant difference was found in activities of 5'-nucleotidase, which is a marker enzyme of cell membrane, in membrane fractions between the hypertensive hearts and the controls, suggesting that the cardiac hypertrophy is not a determinant factor for change in beta-adrenoceptor. The observed decrease in beta-adrenoceptor concentration may reflect an increase in sympathetic nerve activity during development of hypertension. In the chronic stages of hypertension, additional factors may be involved in the restoration of beta-adrenoceptors.
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PMID:Changes in cardiac beta-adrenoceptor concentrations in spontaneously hypertensive and experimental renal hypertensive rats. 627 97

alpha 2-Adrenoceptors were studied in renal membrane fractions from spontaneously hypertensive (SHR), two-kidney, one clip hypertensive (2K, 1C HT) and DOCA-salt hypertensive (DOCA-salt HT) rats, using radioligand binding method. alpha 2-Adrenoceptor concentration in the kidney measured by [3H]yohimbine binding was significantly increased in SHR at 4 weeks old (41.5 +/- 2.8 fmol/mg protein, mean +/- SEM, p less than 0.01), 12 weeks old (54.9 +/- 2.5 fmol/mg protein, p less than 0.01) and 35 weeks old (59.8 +/- 3.4 fmol/mg protein, p less than 0.01) as compared with age-matched Wistar-Kyoto rats (WKY, 31.5 +/- 2.5, 40.9 +/- 1.8, 47.8 +/- 2.0 fmol/mg protein, respectively). There were no significant differences in binding affinity and 5'-nucleotidase activity (plasma membrane marker enzyme) between SHR and WKY at any age. In 2K, 1C HT rats, alpha 2-adrenoceptor concentration in the clipped kidney was higher than that of control rats, but alpha 2-adrenoceptor concentration in the unclipped kidney was unchanged. Binding affinity and 5'-nucleotidase activity showed no significant changes in renal hypertensive rats. In DOCA-salt HT rats, no significant change was found in concentration and affinity of renal alpha 2-adrenoceptor. The observed increase in renal alpha 2-adrenoceptor concentration in SHR may contribute to the pathogenesis and maintenance of hypertension through increased sodium and water reabsorption in the kidney.
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PMID:Changes in renal alpha 2-adrenoceptor in experimental hypertension in rats. 631 79

Hypertension is frequently associated with insulin-dependent diabetes mellitus, but the mechanism of the hypertension is unknown. An animal model of insulin-dependent diabetes mellitus hypertension could be helpful in determining the mechanism, but experimental insulin-dependent diabetes mellitus has been infrequently and irregularly associated with hypertension. In an attempt to develop a dependable model of insulin-dependent diabetes mellitus hypertension, we studied seven series of rats receiving either streptozotocin, surgical reduction of renal mass, or both. We found that superimposing streptozotocin 65 mg/kg body weight on 25% reduced renal mass regularly produced insulin-dependent diabetes mellitus and low-renin volume-expanded hypertension and that the animals remained healthy and hypertensive for as long as followed (13 weeks). Microalbuminuria correlated temporally with blood pressure. We used this dependable model to examine the role of endogenous digitalis-like substance in the development of hypertension in insulin-dependent diabetes mellitus. Plasma levels of digoxin-like immunoreactive factor (DIF), determined with a digoxin radioimmunoassay, were significantly higher in these hypertensive rats than in normotensive control rats (two-kidney diabetic rats, 25% reduced renal mass rats receiving vehicle for streptozotocin). This increase in plasma DIF was associated with a decrease in Na+, K(+)-ATPase activity in microsomes prepared from left or right ventricle. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The plasma DIF level correlated inversely with myocardial Na+, K(+)-ATPase activity and positively with systolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of digitalis-like substance in experimental insulin-dependent diabetes mellitus hypertension. 750 18

We have previously reported that chronic hypertension develops consistently in Wistar rats with a 25% reduction in renal mass (RRM) following the induction of insulin dependent diabetes mellitus (IDDM) with streptozotocin (STZ, 65 mg/kg body weight, intravenously). In this study, we examined the role of the endogenous digitalis-like substance in the development of hypertension. Four groups of rats were studied: 1) 25% RRM rats with STZ-induced IDDM (25-DM), 2) normal rats with STZ-induced IDDM (2K-DM), 3) 25% RRM rats with vehicle treatment (25-V), and 4) normal rats with vehicle treatment (2K-V). In 25-DM rats, blood pressure progressively increased during the 3 weeks after STZ treatment and was associated with microalbuminuria, low plasma renin activity, and extracellular volume expansion. In contrast, the 2K-DM, 25-V, and 2K-V rats remained normotensive. Furthermore, the plasma and urine levels of digoxin-like immunoreactive factor (DIF), determined by digoxin radioimmunoassay (Baxter), were significantly higher in hypertensive 25-DM rats than in their controls. The same was the case for plasma digitalis-like substance (DLS), determined by exposing canine Na+,K(+)-ATPase to plasma fractions and observing the percent inhibition. Increased DIF and DLS in hypertensive 25-DM rats was associated with a significant decrease in Na+,K(+)-ATPase activity of microsomes prepared from the left and right ventricles, when compared with microsomes from normotensive 2K-DM animals. Microsomal 5'-nucleotidase, a plasma membrane marker, was unchanged. The DIF and DLS correlated significantly with each other and with myocardial Na+,K(+)-ATPase activity and mean blood pressure. These results suggest that increased endogenous digitalis-like substance, which inhibits cardiovascular muscle cell Na(+)-K(+)-pump activity, may be involved in the mechanism of hypertension associated with IDDM in 25% RRM rats.
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PMID:Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes in reduced renal mass rats. 839 Feb 68

Adenosine has a major regulatory function in the heart and many tissues. Our previous work showed that a cytosolic (not a membrane, as previously hypothesized) 5'-nucleotidase from dog heart has the kinetic properties consistent with it being the enzyme responsible for adenosine formation from adenosine 5'-monophosphate (AMP) in response to hypoxia or ischemia. In the present study, we evaluated the spatial distribution of AMP-specific cytosolic 5'-nucleotidase in dog heart using electron microscopic immunogold localization. Polyclonal antibodies raised against purified cytosolic 5'-nucleotidase recognized the 43-kd subunit of the enzyme on Western blots of both purified enzyme and the soluble fraction of dog heart homogenates but did not react with proteins extracted from the membrane fraction. Purified cytosolic 5'-nucleotidase and 5'-nucleotidase activity present in the soluble fraction of heart homogenates were inhibited by anti-cytosolic 5'-nucleotidase, but the membrane fraction was not. The monospecific antibodies against the cytosolic 5'-nucleotidase were used for electron microscopic immunogold localization of cytosolic 5'-nucleotidase in dog heart tissue sections. Cytosolic 5'-nucleotidase was found in the cytoplasm of red blood cells, cardiac myocytes, and endothelium; the plasma membrane and interstitium were devoid of gold label. These results are the first to document the presence cytosolic 5'-nucleotidase in specific cell types in the heart and demonstrate the potential for these cell types to produce adenosine via cytosolic 5'-nucleotidase.
Hypertension 1993 Jun
PMID:Immunogold localization of adenosine 5'-monophosphate-specific cytosolic 5'-nucleotidase in dog heart. 850 99

Previous studies have shown that chronic salt loading increased renal interstitial adenosine concentrations and desensitized renal effects of adenosine, a phenomenon that could facilitate sodium excretion. However, the mechanisms responsible for the increased adenosine production and decreased adenosine response are poorly understood. This study examined the effects of the dietary high salt intake on adenosine metabolism and receptor expression in the renal cortex and medulla in Sprague Dawley rats. Fluorescent high-performance liquid chromatography analyses were performed to determine adenosine levels in snap-frozen kidney tissues. Comparing rats fed a normal (1% NaCl) versus high salt (4% NaCl) diet, renal adenosine concentrations in rats fed a high salt diet were significantly higher (cortex: 43+/-3 versus 85+/-4, P<0.05; medulla: 183+/-4 versus 302+/-8 nmol/g wet tissue, P<0.05). Increased adenosine concentrations were not associated with changes in the 5'-nucleotidase or adenosine deaminase activity, as determined by quantitative isoelectric focusing and gel electrophoresis. Western blot analyses showed that a high salt diet (4% NaCl for 3 weeks) downregulated A1 receptors (antinatriuretic type), did not alter A2A and A2B receptors (natriuretic type), and upregulated A3 receptors (function unknown) in both renal cortex and medulla. The data show that stimulation of adenosine production and downregulation of A1 receptors with salt loading may play an important role in adaptation in the kidney to promote sodium excretion.
Hypertension 1999 Jan
PMID:Effect of chronic salt loading on adenosine metabolism and receptor expression in renal cortex and medulla in rats. 1060 Nov 39

The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5'-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, beta-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotension system only.
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PMID:Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart. 1080 8

The activities of the enzymes NTPDase (E.C. 3.6.1.5, apyrase, ATP diphosphohydrolase, ecto-CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) were analyzed in platelets of type 2 diabetic, hypertensive and type 2 diabetic/hypertensive patients. The results showed an increase in platelet NTPDase activity in type 2 diabetic (34% and 72%), hypertensive (32% and 70%) and type 2 diabetic/hypertensive patients (30% and 55%) when compared to control (P<.01) with ATP and ADP as substrate, respectively. 5'-Nucleotidase activity was elevated in the hypertensive (60%) and type 2 diabetic/hypertensive (53%) groups when compared to the control and type 2 diabetic group (P<.01). No differences in sensitivity to inhibitors was detected between the platelets of controls and type 2 diabetic/hypertensive patients. No effects on the enzyme activities were observed when pharmacological doses of propranolol, captopril, furosemide, chlorpropamide, acetylsalicylic acid and glibenclamide were administered. Furthermore, changes in platelet adhesiveness and reactivity were found in all groups tested. In conclusion, we may postulate that NTPDase and 5'-nucleotidase from platelets are altered in patients with type 2 diabetes and hypertension. Probably, such alterations are involved in compensatory physiological responses in these diseases and are related to other important mechanisms of thromboregulation.
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PMID:Enzymes that hydrolyze adenine nucleotides in diabetes and associated pathologies. 1275 73

Age-related changes in adenyl purine release from rat arteries and endothelial cell (EC) plasma membrane (PM) fluidity were studied. High performance liquid chromatography-fluorescence revealed that aging significantly decreased the release of adenyl purines. Pyrene-excimer spectroscopy disclosed that EC PM fluidity of aged rats decreased more significantly than that of young rats. An increase in cholesterol content and a decrease in the unsaturation index (USI) of fatty acids in cholesterol-enriched ECs reduced PM fluidity and 5'-nucleotidase (5'-ND) activity (measured by coupled assay of adenosine deaminase and glutamate dehydrogenase). Moreover, a decrease in cholesterol content and an increase in the USI of fatty acyl chains of the PM in docosahexaenoic acid-enriched ECs concurrently increased enzyme activity and extracellular adenosine. Therefore, decreases in PM fluidity, observed with age-dependent increased cholesterol and decreased USI, induce a decrease in 5'-ND activity, decrease extracellular adenosine levels, and might relate to hypertension in aged rats.
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PMID:Effects of aging on the relation of adenyl purine release with plasma membrane fluidity of arterial endothelial cells. 1616 46

The nucleotide degrading enzymes, ectonucleotidases, present on the platelet surface of human pregnant with a normal (without complications) or high risk for thrombosis (hypertension and gestational diabetes) were studied. NTPDase (E.C. 3.6.1.5, CD39) and 5'-nucleotidase (E.C. 3.1.3.5, CD73) activities of four patient groups, non-pregnant (NP, n = 18), pregnant without complications (P, n = 25), pregnant with hypertension (HP, n = 15) and pregnant with gestational diabetes mellitus (GDP, n = 10), were analyzed. Increased NTPDase activities were observed in the groups P (37.0%, S.D. = 2.03 and 34.0%, S.D. = 3.19), HP (40.0%, S.D. = 3.32 and 56.0%, S.D. = 3.25) and GDP (23.0%, S.D. = 2.30 and 42.0%, S.D. = 2.26) in comparison to the control group NP (p < 0.01, S.D. = 1.92 and S.D. = 2.48) when ATP and ADP were used as substrate, respectively. AMP was used as substrate to determine the 5'-nucleotidase activities, which showed to be elevated in the groups P (45.0%, S.D. = 1.73), HP (54.0%, S.D. = 2.64) and GDP (68.0%, S.D. = 1.69) when compared to the control group NP (p < 0.01, S.D. = 1.26). However, no statistically significant differences were observed between the groups P, HP and GDP. As a consequence, the enhanced ATP, ADP and AMP hydrolysis was ascribed to the pregnancy itself, independent of a normal or high risk for thrombosis. The enhanced NTPDase and 5'-nucleotidase activities in platelets suggest that these enzymes are involved in the thromboregulation process in the pregnancy.
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PMID:NTPDase and 5'-nucleotidase activities in platelets of human pregnants with a normal or high risk for thrombosis. 1755 93


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