Evidence for the Presence in Arterial Walls of Intracellular-Molecular Mechanism for Action of Mineralocorticoids

Kornel, Ludwig; Ramsay, Colin A.; Kanamarlapudi, N.; Travers, Thomas; Packer, W.

doi:10.3109/10641968209061625

Cited by 35 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although mineralocorticoids have been known to induce an increase in membrane sodium channels," this requires protein synthesis with mineralocorticoid action on the nucleus. 16 The lack of a direct action of mineralocorticoids on red blood cell sodium content has also been demonstrated by Stern et al, 17 in cells from normotensive subjects.…”

Section: Discussionmentioning

confidence: 80%

Red blood cell sodium in the DOCA hypertensive pig.

Guthe¹,

Harris²,

Thio³

et al. 1983

Hypertension

View full text Add to dashboard Cite

SUMMARY The influence of deoxycorticosterone acetate (DOCA) on the sodium content of the red blood cell was determined in the pig. DOCA (100 mg/kg), impregnated in Silastic, was implanted subcutaneousty (s.c.) in six male pigs; seven additional pigs received Silastic implants without the DOCA. Those receiving DOCA had an increase in mean arterial pressure (MAP) that was significant in 48 hours and reached a plateau that was 24 mm Hg greater than that of the controls after 15 days. These animals also developed hypokalemia and polydipsia over approximately the same time course. sure often varies with the amount of sodium ingested, this element is thought to play an important role in some types of experimental and clinical hypertension. The mechanism by which sodium causes this effect is not known, but it is the central theme of much research. 12Investigators studying altered electrolyte metabolism of the red blood cell in hypertension have considered the possibility that this abnormality reflects changes that may occur in other tissues such as vascular smooth muscle or the central nervous system, in which the abnormality may play a causal role in the elevated arterial pressure. MIn the current study, we have observed that the development of deoxycorticosterone acetate (DOCA) hypertension in the pig is accompanied by an increase in intracellular sodium content in the red blood cell. Additional studies were carried out to explore possible mechanisms by which DOCA may produce this increase.

show abstract

Section: Discussionmentioning

confidence: 80%

Red blood cell sodium in the DOCA hypertensive pig.

Guthe¹,

Harris²,

Thio³

et al. 1983

Hypertension

View full text Add to dashboard Cite

show abstract

“…Although RU38486 also inhibited upregulation of ANG-I1 receptors by the mineralocorticoid aldosterone, there are reasons to suspect that a portion of aldosterone-stimulated upregulation of ANG-I1 receptors is mediated through Type I corticosteroid receptors. First, Type I as well as Type I1 corticosteroid receptors have been demonstrated in cultured VSMC (Kornel et al, 1982;Meyer and Nichols, 1981;Scott et al, 1987). Second, a previous study has demonstrated that the aldosterone receptor antagonist spironolactone partially prevents the upregulation of ANG-I1 receptors by aldosterone (Ullian et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of enhanced angiotensin II–stimulated signal transduction in vascular smooth muscle by aldosterone

Ullian

Fine

1994

Journal Cellular Physiology

View full text Add to dashboard Cite

We tested the hypothesis that mineralocorticoids potentiate angiotensin II-stimulated phospholipase C activation through an increased number of angiotensin II receptors in cultured rat aortic vascular smooth muscle cells. Exposure of cells to aldosterone for 24 h resulted in concentration-dependent increases in angiotensin II receptor binding. Via studies of angiotensin II displacement by non-peptide receptor antagonists, both basal and upregulated angiotensin II receptors were found to be of the AT1 subtype. Incubation with 1 microM aldosterone resulted in 50-100% enhancement of angiotensin II (100 nM)-stimulated diacylglycerol formation and intracellular calcium mobilization. Exposure to 100 nM 1,25-(OH)2VitD3, which did not upregulate angiotensin II receptors, did not potentiate stimulated inositol phosphate formation. Incubation with aldosterone resulted in potentiation of inositol phosphate formation upon receptor occupation (100 nM angiotensin II) but not upon post-receptor stimulation (25 mM NaF/10 microM AlCl3). Aldosterone did not increase basal phospholipase C activity or content of the inositol trisphosphate precursor phosphatidylinositol-4,5-bisphosphate. These data are consistent with the hypothesis that aldosterone potentiates angiotensin II-stimulated, phospholipase C-dependent intracellular signals solely by coupling to an increased number of angiotensin II receptors. This mechanism may contribute to the sensitized vascular responses to angiotensin II observed in states of mineralocorticoid excess.

show abstract

“…Before we investigated the cortisol effect on Ang II binding, HCASMC were tested for their ability to bind to 1 Figure 3A). A competition binding study showed that radioligand binding was potentially inhibited by unlabeled Ang II and the Ang II type 1 receptor selective antagonist DuP 753; however, PD123319, an Ang II type 2 receptor selective antagonist, had no effect on the binding of [ 125 I]Ang II at doses as high as 1 mol/L ( Figure 3B).…”

Section: Ang II Receptor In Hcasmcmentioning

confidence: 99%

“…These steroids are essential for the maintenance of vascular tone. 1 They can potentiate the vasoconstrictor action of a number of pressor hormones, including ␣-adrenergic agonists and angiotensin II (Ang II). 2 This potentiation is postulated to be mediated by the upregulation of receptors for these pressor hormones in vascular smooth muscle cells.…”

mentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenase in Cultured Human Vascular Cells

1999

View full text Add to dashboard Cite

Abstract-11␤-Hydroxysteroid dehydrogenases (11␤-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. The diminished dehydrogenase activity (cortisol to cortisone) has been demonstrated in patients with essential hypertension and in resistance vessels of genetically hypertensive rats. 11␤-Hydroxysteroid dehydrogenase type 2 (11␤-HSD2) catalyzes only 11␤-dehydrogenation. However, a functional relationship between diminished vascular 11␤-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11␤-HSD2 and 11␤-HSD type 1 (which is mainly oxoreductase, converting cortisone to cortisol) in human vascular smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by upregulating the receptors of pressor hormones such as angiotensin II. We found that physiological concentrations of cortisol-induced increase in angiotensin II binding were significantly enhanced by the inhibition of 11␤-HSD2 activity with an antisense DNA complementary to 11␤-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11␤-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11␤-HSD deficiency and after administration of 11␤-HSD inhibitors, suppression of 11␤-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. In the present study we provide evidence for a mechanism that could link impaired vascular 11␤-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention.

show abstract

Evidence for the Presence in Arterial Walls of Intracellular-Molecular Mechanism for Action of Mineralocorticoids

Cited by 35 publications

References 22 publications

Red blood cell sodium in the DOCA hypertensive pig.

Red blood cell sodium in the DOCA hypertensive pig.

Mechanisms of enhanced angiotensin II–stimulated signal transduction in vascular smooth muscle by aldosterone

11β-Hydroxysteroid Dehydrogenase in Cultured Human Vascular Cells

Contact Info

Product

Resources

About