Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Kessler, Sean P.; Senanayake, P.; Scheidemantel, Thomas S.; Gomos, Janette B.; Rowe, T.; Sen, Ganes C.

doi:10.1074/jbc.m3023472000

Cited by 20 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For immunohistochemistry, the organs were Histochoice preserved and paraffin embedded, cross-sectioned, and deparaffined as described previously (26). Following paraffin removal, the slides were incubated in 10 mM sodium citrate pH 6 at 100°C for 10 min, and then in PBS for 5 min and in blocking solution at 4°C overnight.…”

Section: Micementioning

confidence: 99%

Tissue-Specific and Inducer-Specific Differential Induction of ISG56 and ISG54 in Mice

Terenzi

White

Pal

et al. 2007

J Virol

View full text Add to dashboard Cite

The interferon-stimulated genes (ISGs) ISG56 and ISG54 are strongly induced in cultured cells by type I interferons (IFNs), viruses, and double-stranded RNA (dsRNA), which activate their transcription by various signaling pathways. Here we studied the stimulus-dependent induction of both genes in vivo. dsRNA, which is generated during virus infection, induced the expression of both genes in all organs examined. Induction was not seen in STAT1-deficient mice, indicating that dsRNA-induced gene expression requires endogenous IFN. We further examined the regulation of these ISGs in several organs from mice injected with dsRNA or IFN-␤. Both ISG56 and ISG54 were widely expressed and at comparable levels. However, in organs isolated from mice injected with IFN-␣ the expression of ISG54 was reduced and more restricted in distribution compared with the expression level and distribution of ISG56. When we began to study specific cell types, splenic B cells showed ISG54 but not ISG56 expression in response to all agonists. Finally, in livers isolated from mice infected with vesicular stomatitis virus, the expression of ISG56, but not ISG54, was induced; this difference was observed at both protein and mRNA levels. These studies have revealed unexpected complexity in IFN-stimulated gene induction in vivo. For the first time we showed that the two closely related genes are expressed in a tissue-specific and inducer-specific manner. Furthermore, our findings provide the first evidence of a differential pattern of expression of ISG54 and ISG56 genes by IFN-␣ and IFN-␤.

show abstract

Section: Micementioning

confidence: 99%

Tissue-Specific and Inducer-Specific Differential Induction of ISG56 and ISG54 in Mice

Terenzi

White

Pal

et al. 2007

J Virol

View full text Add to dashboard Cite

show abstract

“…The FVB strains of mice that were used in this study have been characterized previously (10,13) and have the following genotypes: Ts (AceϪ/Ϫ, Tsϩ/ϩ), Gs (AceϪ/Ϫ, Gsϩ/Ϫ) and Pg (AceϪ/Ϫ, Pgϩ/Ϫ). Animals were maintained on a standard rodent diet and sterile tap water, and studies were performed at the age of 4 mo.…”

Section: Micementioning

confidence: 99%

“…The genotype averages that were obtained by duplicate assays from each mouse are reported Ϯ95% confidence interval (CI). Plasma and renal Ang I and Ang II levels both were measured as described previously (13,15). Duplicate assays on a minimum of three plasma pools, each pool obtained from four to five age-matched mice, were averaged and reported Ϯ95% CI.…”

Section: Aldosterone and Ang I And Ii Levelsmentioning

confidence: 99%

“…Histochoicepreserved, paraffin-embedded kidney sections were prepared as described previously (13). The monoclonal mouse anti-rabbit ACE antibody 3C5 (Mono-ACE, River Forest, IL), which recognizes rabbit ACE but not mouse ACE, was applied at 1:25 in PBST blocking solution for 16 h at 4°C (17).…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…To address this question, we produced several strains of mice with tissue-specific expression of ACE with the expectation that such animals would facilitate the distinction between systemic and local RAAS actions. The general strategy was to use tissue-specific promoters to drive the expression of a single ACE isoform in mice with an ACE null FVB background (10,12,13).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Nephron Function in Transgenic Mice with Selective Vascular or Tubular Expression of Angiotensin-Converting Enzyme

Kessler¹,

Hashimoto

Senanayake

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Angiotensin-converting enzyme (ACE) null mice display aberrant renal pathology. Inadequate formation of angiotensin II (Ang II) results in hypotension, loss of fluid homeostasis, lack of urine concentration, and failure to regulate GFR through the tubuloglomerular feedback (TGF) mechanism. For examining the tissue-specific role of ACE in renal structure and regulation of renal filtrate formation, single-nephron GFR, proximal tubular fluid reabsorption, and TGF responsiveness were determined in mice that expressed ACE in only one tissue. Maximum TGF responses in mice that expressed somatic ACE (sACE) in proximal tubule cells (Gs strain) or germinal ACE in the serum (Pg strain) were reduced significantly compared with wild-type (WT) mice. In contrast, TGF responses in mice that expressed sACE in vascular endothelial cells (Ts strain) were not different from control. Single-nephron GFR was reduced in Ts compared with WT mice, but fractional reabsorption and therefore glomerulotubular balance were not distinguishable. BP responses to exogenous Ang I were diminished in Ts, Gs, and Pg mice, whereas those to Ang II were the same in the different strains. Plasma and renal tissue Ang I of all transgenic mouse strains was significantly higher than WT, whereas Ang II levels were generally lower; aldosterone levels were significantly lower than WT in Ts mice but not in the two other transgenic strains. Our results demonstrate that vascular expression of sACE can largely but not completely restore TGF regulation of GFR. Proximal fluid reabsorption in the chronic absence of proximal tubule ACE is normal. C ontrol of fluid homeostasis by the kidneys requires the participation of numerous paracrine agents that act in concert to regulate the formation of a large glomerular ultrafiltrate and the subsequent retrieval of essential constituents along the tubular system. It has been recognized that among these regulatory pathways the renin-angiotensin-aldosterone system (RAAS) seems to play an important and perhaps dominant role (1). Both angiotensin II (Ang II) as the end product of the enzymatic actions of renin and angiotensinconverting enzyme (ACE) and aldosterone, which is secreted in response to Ang II, have profound effects on the absorption of NaCl and water in most segments of the renal nephron. In addition, Ang II is a vasoactive agent that affects GFR by vasoconstrictor actions in glomerular arterioles (2). Tubular absorption and glomerular filtration are linked by the tubuloglomerular feedback (TGF) mechanism. As NaCl concentration rises in the tubular fluid passing the macula densa, for example as a result of a reduction in proximal fluid absorption, vasoconstriction of afferent arterioles occurs, and the resultant change of GFR limits the delivery of fluid to the late nephron (3). It is thought that this tubulovascular cross-talk assists in the preservation of electrolyte balance by limiting sodium excretion. Whereas adenosine acting through A1 adenosine receptors seems to be the direct mediator of this response, a subs...

show abstract

Pathophysiology, Diagnosis, and Treatment of Mineralocorticoid Disorders

Magill

2014

Comprehensive Physiology

View full text Add to dashboard Cite

The renin-angiotensin-aldosterone system (RAAS) is a major regulator of blood pressure control, fluid, and electrolyte balance in humans. Chronic activation of mineralocorticoid production leads to dysregulation of the cardiovascular system and to hypertension. The key mineralocorticoid is aldosterone. Hyperaldosteronism causes sodium and fluid retention in the kidney. Combined with the actions of angiotensin II, chronic elevation in aldosterone leads to detrimental effects in the vasculature, heart, and brain. The adverse effects of excess aldosterone are heavily dependent on increased dietary salt intake as has been demonstrated in animal models and in humans. Hypertension develops due to complex genetic influences combined with environmental factors. In the last two decades, primary aldosteronism has been found to occur in 5% to 13% of subjects with hypertension. In addition, patients with hyperaldosteronism have more end organ manifestations such as left ventricular hypertrophy and have significant cardiovascular complications including higher rates of heart failure and atrial fibrillation compared to similarly matched patients with essential hypertension. The pathophysiology, diagnosis, and treatment of primary aldosteronism will be extensively reviewed. There are many pitfalls in the diagnosis and confirmation of the disorder that will be discussed. Other rare forms of hyper- and hypo-aldosteronism and unusual disorders of hypertension will also be reviewed in this article.

show abstract

Maintenance of Normal Blood Pressure and Renal Functions Are Independent Effects of Angiotensin-converting Enzyme

Cited by 20 publications

References 42 publications

Tissue-Specific and Inducer-Specific Differential Induction of ISG56 and ISG54 in Mice

Tissue-Specific and Inducer-Specific Differential Induction of ISG56 and ISG54 in Mice

Nephron Function in Transgenic Mice with Selective Vascular or Tubular Expression of Angiotensin-Converting Enzyme

Pathophysiology, Diagnosis, and Treatment of Mineralocorticoid Disorders

Contact Info

Product

Resources

About