Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Secretory components of the adrenal medulla were compared in normotensive Wistar-Kyoto (WKY) rats and in stroke-prone spontaneously hypertensive rats (SHRSP) at both 4 and 12 months of age. Noradrenaline, adrenaline, dopamine, neuropeptide Y, and chromogranins A and B were significantly higher in adrenal glands of SHRSP than those of WKY rats at 4 months. At 12 months, the levels of these components in SHRSP had increased even more (about 200% in WKY rats). There was no change in the relative composition of the adrenal "secretory cocktail." Neither the chromogranin A/chromogranin B ratio nor their apparent proteolytic processing in chromaffin granules differed between SHRSP or WKY rats. The lack of a significant change in membrane-bound cytochrome b561 and the small increase in dopamine beta-hydroxylase suggest that the higher levels of secretory components in SHRSP are not simply caused by an increase in the number of chromaffin granules, but possibly by a selective increase in the secretory content of these organelles providing a larger package for quantal release by exocytosis. This may be relevant for the elevation of blood pressure in this strain. The immunological methods described in this paper allow for the first time a determination of the secretory quantal levels in catecholamine storage. This should be useful for further studies in hypertensive models.
Hypertension 1989 May
PMID:An increased pool of secretory hormones and peptides in adrenal medulla of stroke-prone spontaneously hypertensive rats. 256 78

The fluorescent indicator chlortetracycline was used to estimate membrane-bound calcium in mild, untreated hypertensive patients (n = 39) and normotensive controls (n = 42). All participants were black. After incubation with chlortetracycline, platelet-rich plasma was centrifuged into a pellet and fluorescence was measured with a microspectrofluorometer. At an interval of 45 minutes mean fluorescence values were 11% higher in the hypertensive than in the normotensive group (567 +/- 95 vs. 512 +/- 100 counts/sec, p less than 0.02). With both groups of participants combined, a correlation of borderline statistical significance was noted between diastolic blood pressure and chlortetracycline fluorescence (r = 0.213, p = 0.056). In parallel experiments, sodium and potassium concentrations were measured in red blood cells. Intracellular sodium was also significantly higher in the hypertensive group (p less than 0.01). These data indicate that the total cell burden of calcium is increased in the platelets of hypertensive individuals, possibly a result of abnormal cell metabolism of calcium, and further suggest that circulating platelets in hypertensive individuals may be in a hyperaggregable state.
Hypertension 1989 Feb
PMID:Increased membrane-bound calcium in platelets of hypertensive patients. 230 83

Although renin-secreting tumors are rare, they must be considered in the differential diagnosis of hypertension associated with hypokalemia, which occurs commonly in the hypertensive population. The finding of an ovarian renin-secreting tumor emphasizes the potential importance of the ovary as an extrarenal source of renin; the local ovarian renin-angiotensin system may play a key role in reproductive function by regulating vascular reactivity, local blood flow, steroidogenesis and other physiologic effects. In the illustrative case presented, a renin-secreting ovarian leiomyosarcoma was obtained from a women who presented with hypertension and hypokalemia. Plasma prorenin levels were markedly elevated. Tumor excision was quickly followed by a fall in prorenin levels and tumor recurrence was accompanied by an increase in prorenin levels. Active renin concentration in the tumor homogenates was similar to that found in kidney homogenates while the tissue prorenin concentration was approximately 20 times that found in kidney tissue. When cultured for up to 4 weeks, ovarian tumor cells secreted greater than 95% prorenin. Immunoblot analysis demonstrated that tumor renin had a molecular weight of 47,000, similar to that of human recombinant prorenin. Immunohistochemical staining of tumor tissue with antibodies against human renal renin at the electron microscopic level demonstrated the presence of renin primarily in membrane-bound vesicles and rarely in dense-core secretory granules. These findings suggest that prorenin in this ovarian tumor was secreted by the constitutive pathway, which is mediated by these amorphous vesicles.
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PMID:Extrarenal renin-secreting tumors: insights into hypertension and ovarian renin production. 267 94

Approximately 20% of preterm rabbit pups develop spontaneous germinal matrix hemorrhages (GMH). To understand better the pathogenesis of GMH we studied the ultrastructure of germinal matrix (GM) blood vessels in rabbits delivered at gestational day 28. Regardless of luminal size, the walls of most GM vessels had the structural characteristics associated with a blood-brain barrier (BBB) and consisted of endothelial cells and pericytes, surrounded by GM cell processes. Endothelial cells ranged from voluminous to attenuated, with some cells containing intracytoplasmic, membrane-bound vacuoles, and luminal as well as abluminal cytoplasmic projections. Some short interendothelial junctions had no puncta adherentia, whereas long ones often possessed intermittent pores. In two animals with GMH, intact endothelial cells were separated by narrow and wide gaps filled with luminal contents that occasionally extended beyond the interendothelial opening. The basal lamina (BL) was ill-defined, thin, often discontinuous and of low electron density. Smooth muscle cells and collagen were not present, which precluded any classification into arteries, capillaries and veins. Germinal matrix cell processes lacking both micro- and intermediate filaments were haphazardly disposed around the blood vessel walls in place of astrocytic endplates. Recent reports indicate that an astrocytic environment may be necessary for the development of the interendothelial tight junctions and BL. The presence of "glial foot" processes that lack ultrastructural characteristics of mature astrocytes suggests that interendothelial junctions and basal laminae in the vessels of the ganglionic eminence may not have the necessary structural and functional potential to withstand the transmural pressures or the pathophysiological influence of hypertension, hyperosmolarity, sepsis, and other factors known to open the BBB and to contribute to GMH.
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PMID:Ultrastructure of blood vessels in the ganglionic eminence of premature rabbits with spontaneous germinal matrix hemorrhages. 273 55

The effect of changes in dietary sodium intake and of DOC hypertension on plasma atrial natriuretic peptide (PANP), and affinity (Kd) and number (Bmax) of vascular atrial natriuretic peptide binding sites was studied in the rat. There was no difference in PANP between rats on a high or low sodium intake [33.2 +/- 13.9 versus 30.7 +/- 17.3 (s.d.) fmol/ml], Kd [21.1 +/- 2.7 versus 19.7 +/- 4.5 (s.d.) pmol/l] or Bmax [14.8 +/- 1.6 versus 12.6 +/- 1.8 (s.d.) fmol/mg], respectively. In DOC hypertensive rats, PANP was increased compared with control animals [66.1 +/- 32.4 versus 26.4 +/- 9.9 (s.d.) fmol/ml, P less than 0.05] and there was apparent receptor down-regulation [Bmax 7.7 +/- 1.6 versus 19.7 +/- 3.5 (s.d.) fmol/mg, P less than 0.05] with no change in affinity [Kd 15.6 +/- 3.9 versus 18.3 +/- 3.2 (s.d.) pmol/l]. Down-regulation was confirmed when the membrane-bound enzyme 5'-nucleotidase, rather than protein, was used as an index of receptor number. These results suggest that in the rat, atrial natriuretic peptide (ANP) may be important in regulating cardiovascular homeostasis only following non-physiological alterations in sodium and volume status.
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PMID:Rat atrial natriuretic peptide vascular receptor: effect of alterations in sodium balance and of DOC hypertension. 282 98

Angiotensin-converting enzyme (ACE) has been identified as a prominent brush border membrane-bound enzyme of human jejunum. In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril. These investigations resulted in the following findings. The uninhibited enzyme is stable in native membranes in vitro, with a half-life of 195 +/- 7 h. Kinetic analysis of ACE hydrolysis activity revealed the presence of a single enzyme species, which yielded a high Vmax and displayed a Km similar to purified ACE from lung endothelium. Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension. We determined the brush border ACE value of IC50 = 3 X 10(-9) M Ramipril-diacid, which is the same value for serum and lung ACE. Brush border ACE remains 100% inhibited by 10 microM Ramipril during at least 8 days in vitro. The data indicate that ACE is a prominent jejunal brush border enzyme that behaves pharmacologically and kinetically like its peripheral circulation counterpart. This study suggests that high doses of orally administered ACE inhibitors may affect intestinal epithelial function.
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PMID:Human intestinal brush border angiotensin-converting enzyme activity and its inhibition by antihypertensive Ramipril. 283 Nov 5

Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles.
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PMID:Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report. 288 26

Na+ interaction with unsealed human red cell ghosts has been studied by 23Na-NMR relaxation rate (R1) measurements. Data on a total of nine subjects including seven volunteer normotensives (NBP) and two untreated hypertensives (HBP) are presented. Qualitative treatment of the data gives information on the dynamic behavior of Na+ undergoing fast exchange between the free and bound states. The excess longitudinal relaxation rate (delta R)-1 plotted against total [Na+], known as the James-Noggle plot, exhibits different behavior for NBP and HBP ghosts, with a relatively low binding constant of approx. 100 M-1 for HBP (p less than 0.025) compared to a high constant of 500-1000 M-1 for NBP. To associate our NMR data with membrane-bound (Na+ + K+)-ATPase, 23Na relaxation rates were measured in the presence of 5 mM ouabain. James-Noggle plots constructed for ouabain-sensitive excess relaxation rates show the binding for NBP to be even high affinity (greater than 10(3) M-1) but low capacity. These data may suggest that for a given amount of intracellular Na+, the binding affinity could determine the distribution of Na+ between the membrane and cytoplasm, and that the (Na+ + K+)-ATPase which is primarily responsible for the Na+ affinity might assume an abnormal transport mechanism in HBP membranes.
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PMID:23Na-NMR studies of Na+ interaction with human red cell membranes from normotensives and hypertensives. 370

In order to elucidate the mechanisms by which parathyroidectomy (PTX), performed in young spontaneously hypertensive rats (SHR), delays the development and attenuates the level of hypertension, we studied, in vivo, cardiovascular reactivity (CVR, blood pressure response to bolus noradrenaline administration), aortic calcium distribution and cardiac calcium content in SHR with or without parathyroid glands. PTX was performed in 6-week-old animals and experiments were done in pretreated anaesthetized animals 2 and 22 weeks after surgery. A significantly decreased CVR was observed 22 weeks after PTX in SHR-PTX as compared with controls. These data are not specific for hypertensive animals since similar data are also obtained on normotensive Wistar rats treated in an identical fashion. In addition, after PTX in SHR and Wistar rats myocardial (auricle and ventricle) calcium content was more rapidly reduced (after 2 weeks) than aortic membrane-bound and cellular calcium fractions. The present studies established that PTX decreased CVR and alters calcium content and distribution in the cardiovascular systems of rats from hypertensive and normotensive strains. Furthermore, the results confirm a requirement for the parathyroid glands in the pathogenesis of spontaneous hypertension in SHR and for the normal CVR.
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PMID:Parathyroidectomy, cardiovascular reactivity and calcium distribution in aorta and heart of spontaneously hypertensive rats. 376

Abnormalities of platelet aggregation and cyclic nucleotide metabolism are present in hypertension. We observed a greater increase in the level of cyclic adenosine monophosphate (AMP) after prostaglandin E1 (PGE1) stimulation and a lack of decrease of this cyclic nucleotide by epinephrine in platelets from spontaneously hypertensive rats (SHR) as compared to normotensive rats. The difference in cyclic AMP production between SHR and control rats in response to PGE1 is dependent upon platelet exposure to calcium. Since calcium and cyclic AMP are closely related and are both abnormally regulated in hypertension, we have studied the effect of calcium on adenylate cyclase activity. We show here that two forms of endogenous calcium-dependent proteases (membrane-bound and soluble) stimulate the basal activity and the hormonal responsiveness of adenylate cyclase. The sensitivity of calcium-dependent proteolytic control of adenylate cyclase to very-low concentrations of calcium indicates that the regulation may be physiologically important. Furthermore, calcium exerts a greater influence on platelet adenylate cyclase from SHR than on that from normotensive rats. The adenylate cyclase defect seems to be located in the membrane fraction and may, therefore, result from an increase in the activity of the membrane-bound calcium-protease or may be intrinsic to adenylate cyclase itself. The exact site that is sensitive to proteolysis remains to be established.
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PMID:Calcium-dependent proteolytic stimulation of adenylate cyclase in platelets from spontaneously hypertensive rats. 608 83


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