Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the role of the renin-angiotensin system in steroidogenic enzyme expression, the angiotensin-I converting enzyme inhibitor captopril was administered in conjunction with high potassium (K+) or low (Na+) intake to rats for a 7-day period. Northern blot analysis of adrenocortical zona glomerulosa RNA revealed that sodium restriction markedly increased mRNA production of P-450scc (3.1-fold) and P-450(11 beta) (3.4-fold) as well as of the electron donor adrenodoxin (2.0-fold). Captopril combined to the low Na+ diet led to suppression of these effects and, as also seen with captopril alone, further diminished P-450(11 beta) mRNA levels below controls. These responses were accompanied by parallel changes in respective protein levels of the enzymes as indicated by Western blot analyses. Captopril was also shown to inhibit the K(+)-stimulated levels of P-450(11 beta) mRNA (3.3-fold) and protein (1.4-fold) beneath control values (0.6- and 0.8-fold, respectively). On the other hand, increased P-450scc mRNA and protein levels by K+ loading were not affected by captopril treatment. No response was observed in any steroidogenic enzyme expression in zona fasciculata-reticularis following either diet with or without captopril. Thus, the inhibitory effect of captopril on stimulated steroidogenesis seemed to be mediated in part through transcriptional regulation of P450s. In addition, it appeared that P-450(11 beta) expression might be under the control of the renin-angiotensin system in both high K+ and low Na+ diets as opposed to the K+ stimulation of P-450scc where other mechanisms seemed to be involved.
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PMID:Influence of captopril on adrenal cytochrome P-450s and adrenodoxin expression in high potassium or low sodium intake. 137 6

Transgenic rats [TGR; strain name TGR(mRen2)27] harboring the mouse Ren-2 renin gene have been recently generated as a model for the study of primary hypertension that offers the advantage of a clearly-defined genetic alteration. Expression of the mouse Ren-2 gene causes severe hypertension (200 to 260 mm Hg) which is responsive to converting enzyme inhibitors. Compared to control transgene-negative littermates, plasma renin and angiotensin II values are lowered in TGR, whereas plasma prorenin values are strongly elevated. The adrenal gland in TGR shows marked overexpression of mouse renin messenger RNA; in situ hybridization using a 35S-labelled mouse-renin RNA probe reveals that enhanced renin expression is mainly localized to cells of the zona glomerulosa and outer zona fasciculata. Immunohistochemically, renin protein in the TGR adrenal gland is stored in larger quantities than in controls. Adrenal transgene expression probably accounts for most of the elevated plasma prorenin level in TGR, since bilateral adrenalectomy (ADX) causes a significant decrease in prorenin level (318 +/- 79 ng angiotensin I/ml/hr before ADX to 70 +/- 43 ng 4 days after ADX, P less than 0.0005). In the kidney, renin synthesis is almost completely suppressed in TGR. In situ hybridization demonstrates that few juxtaglomerular afferent arterioles express renin. Immunohistochemically, the TGR kidney shows significantly reduced renin and angiotensin II immunoreactivity at the afferent arteriole. Ultrastructural analysis of the afferent arteriolar wall frequently shows the complete absence of renin secretory granules since the granular cells are mostly converted into smooth muscle cells. Beginning at an age of approximately four to six months, TGR develop hypertension-related alterations and pathological lesions in various tissues. In the kidney, the wall thickness of arterioles and arteries is strongly increased, and glomerular lesions including different stages of sclerosis are observed. The thoracic aorta displays a considerable increase in tunica media thickness due to both myocyte hypertrophy and interstitial fibrosis. Coronary arteries and arterioles of the heart are thickened and perivascular fibrosis is observed. The data show that TGR(mRen2)27 transgenic rats display all typical characteristics of hypertensive pathology, making them an interesting model for therapeutic interventions. The fact that these changes occur in animals with a single gene difference to normotensive rats makes them a particularly suitable model for studies on gene-related hypertensive processes.
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PMID:Transgenic rats carrying the mouse renin gene--morphological characterization of a low-renin hypertension model. 159 60

This study examined the long-term actions of atrial natriuretic factor (ANF), at physiological levels, on renal function and mean arterial pressure (MAP) and the importance of Na intake and the renin-angiotensin-aldosterone system in modulating those effects. After a control period, ANF was infused intravenously at a rate of 10 ng.kg-1.min-1 for 7 days, followed by 7 days of 20 ng.kg-1.min-1 and 7 days of recovery. After 7 days of ANF at 10 ng.kg-1.min-1, MAP decreased from 87 +/- 3 to 80 +/- 2 mmHg in normal dogs on low sodium intake (LS, 7 meq Na/day) and from 89 +/- 2 to 79 +/- 2 mmHg in adrenalectomized dogs (ADX, 7 meq Na/day) given constant mineralocorticoid replacement. In both groups, no significant change in glomerular filtration rate (GFR) was observed, although sodium excretion increased transiently. ANF failed to cause significant changes in MAP, GFR, or sodium excretion in normal dogs on high sodium intake (HS, 269 meq Na/day). In LS and HS no long-term effects of ANF on plasma renin activity (PRA) and aldosterone were observed. In ADX, as expected, no change in aldosterone was observed. Thus, in normal and adrenalectomized dogs on LS, chronic ANF infusion caused sustained reductions in MAP. HS markedly attenuated the hypotensive effect of ANF. Our data suggest that the long-term effect of ANF is salt sensitive but that decreases in PRA and aldosterone are not essential for the long-term hypotensive effect of ANF.
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PMID:Atrial natriuretic factor and blood pressure control: role of sodium and aldosterone. 214 93

Renin secretion was stimulated in rats by adrenalectomy (ADX), by treatment with the converting enzyme inhibitor enalapril (MK 421), or by feeding a low salt diet plus furosemide treatment (FUR). Relative amounts of renin mRNA were measured by densitometric Northern blot analysis using a 32P-labeled 700 bp mouse submaxillary gland cDNA fragment as hybridization probe. Renin secretion was measured in isolated kidneys taken from pretreated rats. Treatment resulted in a 4.4-, 7- and 12.7-fold increase in total renin mRNA in kidneys of ADX, MK 421 and FUR rats, respectively. Plasma renin levels increased 5-, 9- and 12-fold in ADX, MK 421 and FUR rats, whereas ex vivo secretion rates from the isolated kidney were 4.7-, 0.5- and 4.2-fold, respectively, that of controls. Thus, a close relationship between increases in renin secretion in vivo (reflected by plasma renin concentration) and renin mRNA exists, whereas secretion rates in the isolated perfused kidney ex vivo change in a non-proportional fashion.
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PMID:Relationship between renin mRNA and renin secretion in adrenalectomized, salt-depleted, or converting enzyme inhibitor-treated rats. 303 10

The aim of this study was to determine whether hyperreninemia in the adrenalectomized (ADX) rat is dependent on renal prostaglandin synthesis, as has been suggested for two other hyperreninemic conditions, Bartter's syndrome and chronic liver disease. Plasma renin concentration (PRC) in anesthetized, ADX rats was significantly increased (delta +480%; p less than 0.001) compared to sham-operated controls. In vivo, indomethacin (10 mg/kg i.v.) significantly reduced PRC of anesthetized, ADX rats after both 45 min (delta -34%; p less than 0.05) and 90 min (delta -47%; p less than 0.05). In vitro renin release from renal cortical slices of ADX rats was also significantly greater (delta +130%; p less than 0.05) than from sham-operated control cortical slices. Renin release from cortical slices of ADX rats given dexamethasone (10 micrograms/kg/day) for 4 days prior to sacrifice did not differ from sham-operated control values. Prostaglandin E2 (PGE2) release from cortical slices of ADX rats did not differ significantly from controls. However, PGE2 synthesis in glomeruli microdissected from ADX rats was significantly increased (delta +110%; p less than 0.001) compared to controls. PGE2 synthesis in glomeruli of dexamethasone-treated ADX rats remained significantly elevated compared to controls. Ibuprofen (10(-6) M) decreased PGE2 synthesis in cortical slices by 80%. However, prostaglandin synthesis inhibition had no effect on renin release from either ADX or control renal cortical slices. These results suggest that despite increased glomerular synthesis, prostaglandins do not directly influence renin release in the ADX rat.
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PMID:Dissociation of hyperreninemia and renal prostaglandin synthesis in the adrenalectomized rat. 351 58

The separate role of mineralocorticoid and glucocorticoid hormone action in maintaining arterial pressure was studied in normotensive rats. Four groups were prepared: adrenalectomized (ADX) rats given 6 micrograms aldosterone/24 h (ALDO; n = 9) or 10 micrograms dexamethasone/24 h (DEX; n = 9) by intraperitoneal Alzet pumps, shamoperated controls (control; n = 10) and ADX rats with no hormone replacement (ADX; n = 9). All groups were given 1% NaCl + 2.5% glucose drinking solution. Measurements of plasma corticosterone and aldosterone and urinary aldosterone excretion confirmed the adequacy of the experimental groups. Forty-eight hours after ADX or sham, base-line intra-arterial mean arterial pressure (MAP) in conscious undisturbed rats was similar in the four groups. Captopril (1 mg/kg iv) produced a similar reduction in MAP in ALDO (-11 +/- 2 mmHg) and DEX (-12 +/- 1 mmHg) groups, despite a lower plasma renin activity (PRA) in ALDO (2.0 +/- 0.7 and 6.0 +/- 1.5 ng X ml-1 X h-1, respectively; P less than 0.05). dP (Me)TyrAVP (50 micrograms/kg iv) caused a greater decrease in MAP in ALDO (-15 +/- 3 mmHg) than in DEX (-8 +/- 1 mmHg; P less than 0.05). Combined blockade with both antagonists resulted in a greater MAP reduction in ALDO (-29 +/- 4 mmHg) than in DEX (-15 +/- 4 mmHg; P less than 0.05). These results indicate that glucocorticoid hormone action maintains arterial pressure in ADX rats by mechanisms similar to normal rats and largely independent of the renin-angiotensin system and vasopressin. In contrast, mineralocorticoid replacement alone in ADX rats requires increased participation of both peptide systems for maintenance of arterial pressure.
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PMID:Role of mineralocorticoids and glucocorticoids in blood pressure regulation in normotensive rats. 353 7

The relative hypertensinogenic potencies of recently synthesized 19-nor-aldosterone and its precursor 19-OH-aldosterone were assessed in comparison to that of aldosterone (Aldo) in young (6-week-old) adrenalectomized (ADX) spontaneously hypertensive rats (SHR). Infusion of 19-nor-aldosterone for 2 weeks by Alza mini-osmotic pumps caused significant, dose-dependent increases in the systolic blood pressure (BP) of young ADX SHR; dosages of 0.1 and 0.5 microgram/day raised the BP from 127 +/- 2 mmHg to 164 +/- 9 and 180 +/- 11 mmHg, respectively. During this period, control ADX SHR receiving vehicle only remained normotensive. Similar increases in BP were seen only with infusion of slightly higher dosages of Aldo (0.5 and 1.0 micrograms/day). In contrast, 19-OH-aldosterone infused at higher dosages (10 or 25 micrograms/day) caused little change in BP of ADX SHR. Full suppression of plasma renin activity (PRA) was observed with 0.1 and 0.5 microgram/day 19-nor-aldosterone, whereas Aldo caused similar decreases in PRA only at dosages of 0.5 microgram/day and higher. Interestingly, although infusions of 19-OH-aldosterone did not cause a significant change in BP, these dosages (10 and 25 micrograms/day) significantly suppressed PRA. These studies which show that 19-nor-aldosterone is equipotent to Aldo, and perhaps slightly more active in ADX SHR, indicate that 19-nor-aldosterone is a potentially important hypertensinogenic steroid.
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PMID:The effects of 19-nor-aldosterone on blood pressure of adrenalectomized spontaneously hypertensive rats. 384 21

The origin and regulation of angiotensinogen in cerebrospinal fluid (CSF) was investigated in rats by measuring renin substrate in plasma and CSF under different experimental conditions. Nephrectomy (NX) increased the circulating and the central angiotensinogen levels. There was no correlation between the individual values of plasma and CSF. Adrenalectomy (ADX) diminished and hydrocortisone treatment augmented the angiotensinogen levels in plasma and CSF. The combination of ADX and NX caused a dissociation between peripheral and central angiotensinogen, since the values were elevated in plasma but unchanged in CSF. After the application of the converting-enzyme inhibitor captopril a significant decrease of angiotensinogen was observed in plasma only. A specific radioimmunoassay for renin substrate of rat plasma also recognized CSF angiotensinogen. There was a linear correlation between the CSF substrate levels obtained by direct and indirect measurement. In conclusion, CSF angiotensinogen appears to be immunologically similar to the plasma molecule. The angiotensinogen levels in CSF and plasma may be affected in parallel but can nevertheless be dissociated from each other.
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PMID:Regulation of angiotensinogen in cerebrospinal fluid and plasma of rats. 634 May 30

Several interventions known to alter plasma renin substrate in rats such as nephrectomy (NX), adrenalectomy (ADX) and glucocorticoid treatment changed the angiotensinogen content in the cerebrospinal fluid (CSF) in the same direction. However, peripheral and central angiotensinogen could be dissociated from each other by ADX and NX in combination, as well as by chronic converting enzyme blockade. The regulation of brain angiotensinogen was further investigated in stroke-prone spontaneously hypertensive rats (SHR-sp) in comparison with normotensive Wistar Kyoto (WKY) rats. The angiotensinogen levels of the anterior hypothalamus and of the septal area showed strain and age-related differences. Chronic converting enzyme blockade, which kept SHR-sp normotensive, stimulated angiotensinogen in the anterior hypothalamus of both SHR-sp and WKY rats, but suppressed plasma renin substrate. A specific radioimmunoassay (RIA) for renin substrate of rat plasma also recognized the CSF angiotensinogen, and a linear correlation existed between direct and indirect measurements. In conclusion, angiotensinogen in the central nervous system appears to be immunologically similar to plasma angiotensinogen. Its regulation is not directly related, however, to circulating renin substrate, although adrenal steroids stimulate both central and peripheral angiotensinogen. A differential regulation of angiotensinogen in the brain of SHR-sp as compared to WKY is evident and could be linked to blood pressure control.
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PMID:Regulation of angiotensinogen in the central nervous system. 635 57

The development of hypertension in spontaneously hypertensive rats (SHR) was blocked by adrenalectomy and restored with aldosterone treatment. The blood pressures of normotensive strains of rat were not affected by aldosterone. Infusions of 10 micrograms aldosterone/day into adrenalectomized (ADX)--SHR, Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats completely suppressed plasma renin activity in all strains and lowered plasma potassium levels to below normal in WKY and SD rats; aldosterone treated SHR were normokalemic. In acute studies, SHR responded normally to the antinatriuretic actions of aldosterone but gave a shallower kaliuretic response compared with WKY and SD rats. The urine of ADX-SHR injected with 3H-aldosterone contained a larger proportion of polar neutral metabolites of aldosterone than WKY urine but smaller amounts of acidic and sulfate metabolites. HPLC of the neutral metabolites showed that several polar compounds were present in larger amounts in SHR urine but that unmetabolized aldosterone was less than in WKY urine.
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PMID:Aldosterone and its metabolism in spontaneously hypertensive rats (SHR). 675 47


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