11β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN MESENTERIC ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS

Takeda, Yoshiyu; Yoneda, Takashi; Miyamori, Isamu; Gathiram, P.; Takeda, Ryuji

doi:10.1111/j.1440-1681.1993.tb01644.x

Cited by 21 publications

(9 citation statements)

References 27 publications

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“…Decreased 11␤-HSD activity has been demonstrated in some patients with essential hypertension [1][2][3] and in rats with genetic hypertension. 4,5 Biochemical studies have revealed the existence of 2 isoforms of 11␤-HSD: NAD ϩ dependent and NADP ϩ dependent. 11␤-HSDII (the NAD ϩ -dependent isoform) is found in distal portions of the nephron, where it has been shown to colocalize with mineralocorticoid receptors.…”

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confidence: 99%

Renal 11β-Hydroxysteroid Dehydrogenase in Genetically Salt-Sensitive Hypertensive Rats

1998

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Abstract-Renal 11␤-hydroxysteroid dehydrogenase II (11␤-HSDII) converts glucocorticoids into inactive metabolites and plays an important role in controlling blood pressure and sodium retention. To examine whether this enzyme may be involved in the pathophysiology of salt-sensitive hypertension, we determined 11␤-HSDII activity and mRNA levels in the blood vessel and kidney of Dahl Iwai salt-sensitive (DS) rats and Dahl Iwai salt-resistant (DR) rats. Urinary free corticosterone:free 11-dehydrocorticosterone ratio was measured to estimate renal 11␤-HSD activity. Vascular 11␤-HSDII activity was expressed as percent conversion of [ 3 H]corticosterone to [ 3 H]11-dehydrocorticosterone in homogenized mesenteric arteries. 11␤-HSDII mRNA was estimated with the use of competitive polymerase chain reaction (PCR). Renal 11␤-HSDII activity and mRNA levels were significantly decreased in 8-and 12-week-old high salt DS rats compared with DR, Sprague-Dawley (SD), or low salt DS rats of the same age. Decreased 11␤-HSDII activity and mRNA levels in mesenteric arteries were observed in 8-and 12-week-old high salt DS rats. Urinary excretion of 11␤-HSDII inhibitory factors was measured by inhibition of enzyme activity in microsomes from human kidney. The urinary inhibitors were significantly increased in 8-and 12-week-old high salt DS rats compared with DR, SD, or low salt DS rats of the same age. There were no significant differences in 11␤-HSDII activity and mRNA levels in mesenteric arteries and kidney or in urinary inhibitors between 4-week-old DS, DR, and SD rats. These results indicate that 11␤-HSDII may play a role in salt sensitivity and development of hypertension in the DS rat.

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Renal 11β-Hydroxysteroid Dehydrogenase in Genetically Salt-Sensitive Hypertensive Rats

1998

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“…The authors (19) demonstrated the expression of 1119-HSD in the mesenteric artery by immunocytochemical staining methods, in situ hybridization, and by Northern blot analysis. Therefore, it is likely that 1119-HSD activity is diminished at the site of resistance vessels per se, as we demonstrated for the mesenteric artery of spontaneously hypertensive rats (21). If this is true in primary hypertension, the vasoconstrictor response to cortisol would be potentiated, even in minor stressful conditions, through the enhanced binding of cortisol to the mineralocorticoid receptor.…”

Section: Altered Steroid Metabolismmentioning

confidence: 80%

Endocrine and Auto-Paracrine Factors in the Pathogenesis of Primary Hypertension.

Takeda

Miyamori

1995

Hypertens Res

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Referring to the mosaic theory of Page, the authors present an overview of recent topics related to the participation of endocrine and auto-paracrine factors, such as steroids, ouabain-like substance, insulin, renin-angiotensin and endothelin, in the pathogenesis of primary hypertension. These factors promote the development of hypertension in either a direct or indirect manner; in addition, they promote, to some extent, the proliferation of vascular smooth muscle cells. Future research should attempt to elucidate interactions between these factors in cardiovascular tissues and to define how these factors interact with various vasodepressor substances to regulate blood pressure. (Hypertens Res 1995; 18: 171-179) Key Words: steroids, ouabain-like substance, insulin, renin-angiotensin, endothelin, primary hypertension Although primary hypertension accounts for 95% of all cases of hypertension, the multifaceted mosaic concept for the pathogenesis of this disease, proposed by Page (1) in 1963, still remains valid. One can only say that a number of new facets, which integrate closely into the mosaic theory, have appeared during the past few decades.The blood pressure can be defined as the product of cardiac output (pumping action of the heart) and peripheral resistance (arterial tone) . Moreover, complex mechanisms, involving interactions among genetic, hormonal and physical factors, affect each of the determinants. Recently, the potential roles of various hormones in modulating arterial tone, not only by the functional regulation of resistance vessels but also by their structural alterations (remodeling), have attracted considerable interest. The reason for revived interest in the hormonal aspects of the pathogenesis of primary hypertension seem to be due, in part, to the discovery of new vasoactive substances derived from the vascular tissue, acting as an auto-paracrine organ. Assuming a certain subgroup of primary hypertension can be identified as being caused by a state of vasopresssor hormone excess or dilator deficiency, that subgroup then should be categorized as a form of secondary (endocrine) hypertension.In the present review, the authors present an overview of recent advances in endocrinological aspects of primary hypertension and address questions that have emerged as a result of advances in the research of altered steroid metabolism, ouabainlike substances, the renin-angiotensin-aldosterone system, and endothelin. Altered Steroid MetabolismDuring the 1960s and 1970s, Kornel et al. (2-4) reported a series of articles suggesting that altered cortisol metabolism results in increased excretion of polar derivatives of cortisol (non-A-ring-reduced 20-hydroxysteroids and 6R-hydroxysteroids). They also provided some evidence for the predominant role of sulfoconjugation rather than glucuronoconjugation in primary hypertension. However, the precise implications of these findings in the pathogenesis of primary hypertension are still unclear.Recently, the pathophysiological importance of cortisol inactivation by...

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“…[11][12][13][14][15][16] Although the kidney plays a major role in sodium homeostasis and has often been implicated in the pathogenesis of hypertension, no differences of renal 11␤HSD were observed between Milan hypertensive rats and their normotensive counterparts, 11 whereas 11␤HSD activity was found to be increased in mesenteric arteries and decreased in the hearts of SHR. 13,14 Recently, the decrease of renal 11␤HSD was reported in hypertensive DS in comparison with the normotensive DR rats.…”

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“…However, it has recently been reported that the mesenteric enzyme activity is significantly decreased in both SHR and DS-HS rats compared with their normotensive counterparts. 12,14 It means that there are not uniform changes in enzyme activity in different parts of the cardiovascular systems of normotensive and hypertensive rats or that the differences result from differences in techniques used (homogenate v perfusion of isolated arteries). The reaction direction of 11␤HSD (11␤HSD-1) depends on the cell context/local environment and therefore the direction of the reaction in homogenate does not always reflect the activity of the intact tissue.…”

Section: Fig 3 11␤hsd Activity In Ds and Dr Rats Fed A High-salt DImentioning

confidence: 99%

11 -hydroxysteroid dehydrogenase activity in spontaneously hypertensive and Dahl rats

Pohlová

Mikšı́k

Kuneš

et al. 2000

American Journal of Hypertension

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The role of the enzyme 11␤-hydroxysteroid dehydrogenase (11␤HSD) in hypertension remains unknown even if it appears that the inappropriately decreased 11␤HSD activity might be involved in a process that leads to high blood pressure. The possible changes of 11␤HSD were therefore investigated in rats with spontaneous or salt-induced hypertension. The adult male rats of the following genotypes were used: spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), Dahl salt-sensitive rats fed either a high-salt diet containing 8% NaCl (DS-HS) or low-salt diet containing 0.2% NaCl (DS-LS), and Dahl saltresistant rats fed the same diets (DR-HS, DR-LS). 11␤HSD was investigated in colon, aorta, renal cortex, and renal medulla and was assessed as percentage conversion of The results demonstrated that genotype exerts a significant effect on 11␤HSD. 11␤HSD activity was significantly increased in colon and renal medulla of SHR compared with WKY rats. No significant differences were observed in renal cortex and aorta. In Dahl rats kept on a low-salt diet, 11␤HSD activity was significantly higher in colon, renal medulla, and cortex of DS-LS than in DR-LS rats but no difference was observed in aorta. The differences disappeared in age-matched DS and DR rats fed the high-salt diet. Increased dietary sodium intake stimulated the activity of 11␤HSD in renal cortex and medulla of DR rats and decreased the activity in colon of DS rats. We conclude that the development of spontaneous and salt-induced hypertension is not associated with decreased activity of 11␤HSD. However, the results showed that salt intake is able to modulate the activity of 11␤HSD and that 11␤HSD in DS and DR rats responds to high dietary salt intake in a different manner. T he enzyme 11␤-hydroxysteroid dehydrogenase (11␤HSD) catalyses the conversion of C-11 hydroxylated glucocorticoids, including cortisol (the primary glucocorticoid in humans), to the 11-oxo metabolites (cortisone, 11-dehydrocorticosterone sues differ in enzyme distribution, cosubstrate dependencies, glucocorticoid affinities, and reaction reversibility. [3][4][5] The NADP-dependent isoform (11␤HSD-1) is a widely expressed enzyme that shows both oxidative and reductive activities and has a relatively low affinity for glucocorticoids. 11␤HSD-2, more recently described, is a NAD-dependent isoform that has high affinity for glucocorticoids, operates only in an oxidative direction, and is localized predominantly in mineralocorticoid target tissues (eg, kidney) and placenta. A congenital deficiency of 11␤HSD (syndrome of apparent mineralocorticoid excess) or inhibition of 11␤HSD by ingestion of licorice or carbenoxolone leads to the activation of mineralocorticoid receptors by glucocorticoids, excessive sodium retention, and hypertension. 6 In addition, it has been shown that many patients with essential hypertension have altered cortisol-to-cortisone conversion. 7Several differences in corticosteroid metabolism have also been described between normotensive and hypertensive strains ...

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11β‐HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN MESENTERIC ARTERIES OF SPONTANEOUSLY HYPERTENSIVE RATS

Cited by 21 publications

References 27 publications

Renal 11β-Hydroxysteroid Dehydrogenase in Genetically Salt-Sensitive Hypertensive Rats

Renal 11β-Hydroxysteroid Dehydrogenase in Genetically Salt-Sensitive Hypertensive Rats

Endocrine and Auto-Paracrine Factors in the Pathogenesis of Primary Hypertension.

11 -hydroxysteroid dehydrogenase activity in spontaneously hypertensive and Dahl rats

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