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)

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

The current investigation was designed to study the effect(s) of high calcium diet on the development of high blood pressure (BP) in both young intact spontaneously hypertensive rats (SHRs) and in young adrenalectomized (ADX) male SHRs treated with aldosterone (ALDO). Weaned SHRs were fed either a control calcium diet (0.5% Ca as PO4) (CCaDiet), a high calcium diet (2.5% Ca, 0.5% as PO4 and 2% as CO3) (HCaDiet), or Agway ProLab rat food containing 2.5% Ca (HCaPLDiet). The HCaDiet significantly blunted the development of high BP in young intact SHRs (P less than 0.001; n = 8 to 10). At 6 weeks of age, BP was 117 +/- 2 mm Hg (HCaDiet) compared with 135 +/- 3 mm Hg (CCaDiet); by 12.7 weeks of age, BP was 192 +/- 4 mm Hg (HCaDiet) compared with 233 +/- 3 mm Hg (CCaDiet). Similar results were observed in age-matched SHRs fed the HCaPLDiet. The results show that subcutaneous infusion of ALDO (1.0 microgram/d, osmotic pumps) for 2 weeks to young ADX male SHRs raised on the CCaDiet caused a significant increase in systolic BP when compared with SHRs implanted with Sham pumps (P less than 0.001). High BP associated with ALDO infusion was attenuated by the HCaDiet (BP after 2 weeks was 138 +/- 8 mm Hg for the HCaDiet group compared with 200 +/- 5 mm Hg for the CCaDiet group, P less than 0.001; n = 4 to 6). The results show that the HCaDiet blunts the development of high BP in intact SHRs and may protect against the development of ALDO hypertension in ADX young SHRs.
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PMID:Effect of high calcium diet on the development of high blood pressure in intact spontaneously hypertensive rats and in adrenalectomized spontaneously hypertensive rats treated with aldosterone. 204 31

19-Nor-deoxycorticosterone (19-nor-DOC) is a mineralocorticoid that is increased in some forms of experimental and human hypertension. The pivotal step in 19-nor-DOC biosynthesis is adrenal P450 19-hydroxylase, but this enzyme has not been clearly distinguished from P450 11 beta/18-hydroxylase. This study attempted to specifically inhibit adrenal 19-hydroxylation of deoxycorticosterone (DOC) using a suicide aromatase inhibitor, 19-acetylenic androstenedione (19-AA). Purified bovine P450 11 beta/18/19-hydroxylase was incubated with excess substrate DOC, adrenodoxin, and adrenodoxin reductase in the presence of increasing doses of the inhibitor, 19AA. 11 beta-, 18-, and 19-hydroxylation were measured by quantification of corticosterone, 18-OH-DOC, and 19-OH-DOC respectively. Measurements of these products demonstrated that 11 beta- and 18-hydroxylation was not inhibited whereas 19-hydroxylation was inhibited as manifested by decreased 19-OH-DOC formation (p less than .05). The IC50 of 19-AA was approximately 10(-12) M. The specific inhibition of 19-hydroxylation suggests that the 19-hydroxylase may be an enzyme distinct from the P450 11 beta/18-hydroxylase. This further suggests that 19-nor-DOC biosynthesis may be under independent regulation and may be amendable to specific in vivo inhibition.
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PMID:19-Hydroxylase inhibition of adrenal mitochondrial P450 11 beta/18/19-hydroxylase by a suicide inhibitor. 278 64

Circulating levels of 11-deoxycorticosterone are increased during the development of adrenal-regeneration hypertension. The present studies were undertaken to examine the mechanisms involved in this increase. Plasmids containing cDNA inserts coding for cytochrome P-45011 beta, cytochrome P-450scc and adrenodoxin were used to determine, by Northern blot analysis, mRNA levels at 1, 2 and 3 weeks of adrenal regeneration. There was a striking decrease in mRNA transcripts for all three enzymes during the first week of regeneration when compared with intact adrenal tissue. Over the next 2 weeks the mRNA levels increased to 64% for P-45011 beta, to 80% for P-450scc and to 82% for adrenodoxin. Actin mRNA levels were 70% of control levels in the first week but were back to control levels by the second week. The present findings suggest that decreased expression of steroid 11 beta-hydroxylase could contribute to the increased secretion of 11-deoxycorticosterone during the early stages of adrenal regeneration.
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PMID:Cytochromes P-45011 beta, P-450scc and adrenodoxin gene expression during adrenocortical regeneration in the rat. 278 99

The effect of selective glucocorticoid or mineralocorticoid deficiency upon arterial pressure was evaluated in unanesthetized adult spontaneously hypertensive rats (SHR). Adrenalectomized SHR were replaced with 6 micrograms/24 h aldosterone (ALDO), 10 microgram/24 h dexamethasone (DEX), or both aldosterone and dexamethasone (ALDO + DEX) by IP osmotic mini-pumps. These were compared to sham-operated SHR (SHAM) and adrenalectomized SHR given no steroid replacement (ADX). Drinking fluid for all groups was 1% NaCl + 2.5% glucose. Six days after adrenalectomy, intra-arterial mean arterial pressure (MAP) fell from 174 +/- 2 to 149 +/- 6 mm Hg in ALDO (n = 8, P less than .01) and from 179 +/- 4 to 125 +/- 4 in ADX (n = 6, P less than .01). In contrast, MAP rose in SHAM from 171 +/- 4 to 179 +/- 5 mm Hg (n = 7, P less than .01), in ALDO + DEX from 161 +/- 3 to 184 +/- 4 mm Hg (n = 7, P less than .01), and in DEX from 162 +/- 2 to 181 +/- 4 mm Hg (n = 7, P less than .01). The results indicate that when diet salt intake is high, glucocorticoid action is necessary for the full expression of hypertension in adult SHR.
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PMID:Effect of glucocorticoid deficiency on arterial pressure in conscious spontaneously hypertensive rats. 291 51

Treatment of rats with methylandrostenediol (MAD), an anabolic androgen, caused a profound reduction (65%) in the level of cytochrome P-450 11 beta in rat adrenocortical mitochondria as measured by immunoblots using a specific antibody. The decreases in mitochondrial cytochrome P-450scc (15%) and adrenodoxin (20%) were much less than that observed for cytochrome P-45011 beta. A 35% decrease in adrenal microsomal cytochrome P-450 21 and NADPH-cytochrome P-450 reductase levels was brought about by the treatment with MAD. The data establish that the preferential decrease in adrenal steroid 11 beta-hydroxylase activity associated with androgen treatment results from a decrease in cytochrome P-450 11 beta. This is consistent with the role of 11-deoxycorticosterone in the pathogenesis of androgen-induced hypertension in rats.
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PMID:Levels of adrenodoxin, NADPH-cytochrome P-450 reductase and cytochromes P-45011 beta, P-45021, P-450scc, in adrenal zona fasciculata-reticularis tissue from androgen-treated rats. 312 24

The effect of coarctation of the abdominal aorta (AC) and of sham operation (SO) on the development of myocardial hypertrophy was studied in three groups of male rats, i.e., a group without treatment prior to AC or SO (untreated), a group with bilateral adrenalectomy (ADX) 5-7 days before AC or SO, and a group in which the adrenal medulla was removed (MDX) 5-7 days before AC or SO. MDX resulted in functional elimination of the adrenal medulla without apparent effect on cortical function. The animals were killed 7-10 days after AC or SO. AC produced carotid blood pressure (CBP) increases of 33, 31, and 25 mmHg in the untreated, ADX, and MDX groups, respectively. Ventricular weight (HW), ventricular RNA concentration, and RNA-to-DNA ratio increased significantly after AC only in the untreated and MDX groups. In the ADX group, hypertension was followed by an increase in HW that could be detected only after normalization for body weight. It is concluded that absence of the adrenal gland significantly reduces the development of pressure-induced myocardial hypertrophy. Apparently, this is due to the absence of the adrenal cortex and not absence of the adrenal medulla.
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PMID:Role of adrenals on development of pressure-induced myocardial hypertrophy. 621 59

We studied the effect of changing perfusion pressure on the excretory function of isolated perfused nonclipped kidneys from the two-kidney Goldblatt hypertensive rat ( GHR ). Kidneys were studied from newly hypertensive rats about 8 days after contralateral renal artery clipping [blood pressure (BP) 138 +/- 4.3 mmHg] and before onset of hypertension 3 days following surgery (BP 111 +/- 1.9 mmHg). In addition, nonclipped kidneys from adrenalectomized Goldblatt rats were also examined approximately 9 days following surgery (BP 114 +/- 4.7 mmHg). Kidneys from sham-operated rats served as controls. We noted no differences in GFR in kidneys from newly hypertensive rats and sham controls above a perfusion pressure of 120 mmHg. In response to increasing perfusing pressure, perfusate flow and fractional sodium excretion were significantly lower in newly hypertensive rats than in sham-operated controls. No differences in glomerular filtration rate, perfusate flow, or sodium excretion were noted in kidneys from sham-operated rats or Goldblatt rats 3 days following surgery. After clipping, adrenalectomized (ADX) Goldblatt rats had less of a rise in blood pressure than did rats with intact adrenal glands. No attenuation of natriuresis was noted in the ADX-clipped group in response to increasing perfusion pressure. Isolated perfused kidneys from ADX rats had greater sodium excretion at all levels of pressure than kidneys from rats with intact adrenal glands. Deoxycorticosterone acetate replacement returned sodium excretion to that approaching intact rats. We conclude that nonclipped kidneys of newly hypertensive Goldblatt rats exhibit blunted pressure natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Attenuated pressure natriuresis in the early phases of two-kidney Goldblatt hypertension. 672 Sep 72

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

A continuous sc infusion of aldosterone for 2 weeks (10 micrograms/day) markedly increased the blood pressure of male, adrenalectomized (ADX), spontaneously hypertensive rats (SHR) from 142 to 178 mm Hg, which was similar to the increase seen in a group of sham-operated SHR. The blood pressure in a group of ADX SHR maintained without aldosterone declined from 141 to 119 mm Hg during the 2 weeks after surgery. Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats treated in an identical fashion remained normotensive throughout. Adrenalectomy caused hyperkalemia in all strains of rat. Plasma potassium levels in aldosterone-treated WKY and SD rats were lower than those in sham-operated controls, but were similar to those in corresponding groups of SHR. Acute renal responses of ADX male rats showed that SHR reabsorbed more water and sodium of an injected isotonic saline load than WKY rats and excreted less potassium than either WKY or SD rats. Sensitivity to aldosterone in the three strains of rats was compared using the urinary sodium to creatinine and potassium to creatinine ratios 1-3 h postinjection of aldosterone. Decreases in the urinary ratio of sodium to creatinine in response to various doses of aldosterone (0-1.25 micrograms aldosterone) were similar for the three strains of rat. ADX SHR appeared to be less responsive to the kaliuretic actions of aldosterone than WKY and SD rats. The present studies show that aldosterone is essential to the development of hypertension in SHR. The hypertensinogenic actions of aldosterone in these rats may be related to a blunted kaliuretic response to mineralocorticoids.
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PMID:The role of aldosterone in the development of hypertension in spontaneously hypertensive rats. 730 34


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