Renin and angiotensinogen gene expression in maturing rat kidney

Abstract

To determine whether angiotensinogen (Ao) and renin are synthesized by the immature kidney and to assess the changes in intrarenal renin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and Ao relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and Ao cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I.h-1.mg protein-1 in the incubation media. RRC was higher in newborn than in adult SHR (979 +/- 164 vs. 206 +/- 47) and WKY (573 +/- 69 vs. 297 +/- 74) (P less than 0.05). In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animal. Ao mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and Ao genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

The Kidney Androgen-regulated Protein Promoter Confers Renal Proximal Tubule Cell-specific and Highly Androgen-responsive Expression on the Human Angiotensinogen Gene in Transgenic Mice

“…Our understanding of the RAS in normal and pathophysiological regulation of blood pressure has been complicated by the fact that in addition to its actions as an endocrine system, certain individual tissues, such as the kidney (5-7), heart (8, 9), brain (10), and vasculature (11), contain all the components of the RAS cascade and therefore have the potential for local synthesis and action of Ang-II. In the kidney, for example, renin, AGT and ACE mRNAs, and proteins are synthesized in juxtaglomerular cells, proximal convoluted tubule (PCT) cells, and endothelial and tubular cells, respectively, and Ang-II type-1 (AT-1) and type-2 (AT-2) receptors are localized in glomeruli, collecting ducts, tubules, and vasa recta (12)(13)(14)(15)(16)(17)(18). The intrarenal RAS has been postulated to regulate various aspects of renal function including blood flow, natriuresis, and tubular-glomerular feedback, and may therefore participate in the pathogenesis of hypertension (19 -21).…”

Renin-angiotensin system in the kidney: What is new?

“…Ang Ⅱ also acts through intracellular receptors. Local RAS was first described within the kidney over 20 years ago [29][30][31][32] , where the levels of Ang Ⅱ are much higher than in plasma [32,72] . Intrarenal Ang Ⅱ levels and local formation in the kidney have been reported by Navar and colleagues [11,32,[73][74][75][76] .…”

“…It is now considered that RAS assumes paracrine, autocrine and intracrine mechanisms of action in hormone signaling [6,28] . Many tissues and cells, including kidneys, have all the necessary RAS components to form Ang Ⅱ in situ [29][30][31] . Renal levels of Ang Ⅱ are much higher than in the plasma [32] , indicating that the source of Ang Ⅱ within the kidney is not only provided by filtered plasma Ang Ⅱ.…”

“…Renal levels of Ang Ⅱ are much higher than in the plasma [32] , indicating that the source of Ang Ⅱ within the kidney is not only provided by filtered plasma Ang Ⅱ. The kidney expresses all the major components of the RAS, such as angiotensinogen, renin and ACE [29][30][31] . Locally synthesized Ang Ⅱ can act on cell surface, nuclear and cytoplasmic AT1 and AT2 receptors [33][34][35] .…”

Developmental Changes in Expression of Angiotensinogen mRNA in Rat Nephron Segments.

“…The intrarenal expression of renin, angiotensin-converting enzyme, and angiotensinogen mRNAs has been demonstrated by Northern blot analysis (1-6, 14), and the intrarenal tissue sites of renin and angiotensinogen mRNA synthesis have been localized by in situ hybridization (15)(16)(17) . Furthermore, studies using reverse transcription and polymerase chain reaction (RT-PCR) have shown the localization of angiotensin II type 1 receptor and angiotensinogen mRNA in microdissected nephron segments (18).…”