Contribution of angiotensin II internalization to intrarenal angiotensin II levels in rats

Abstract

This study was designed to determine the involvement of AT(1) receptors in the uptake of ANG II in the kidney of rats exposed to differing salt intake. Male Wistar-Kyoto rats were treated with a normal-salt (NS; 1% NaCl, n = 7) or a low-salt (LS; 0.025% NaCl, n = 7) diet combined with (LS+Los, n = 7; NS+Los, n = 7) or without losartan (30 mg. kg(-1). day(-1)), an AT(1) receptor antagonist. Renin (RA) and angiotensin-converting enzyme (ACE) activities and angiotensinogen, ANG I, and ANG II levels were measured in plasma, renal cortex, and medulla. In LS rats, in both plasma and renal cortex, the increase in RA was associated with an increase in ANG I and ANG II levels compared with NS rats, but intrarenal ANG II levels increased more than ANG I levels. In NS+Los rats, the increase in RA in plasma was followed by a marked increase in plasma ANG I and ANG II levels compared with NS rats whereas in the kidney the increase of renal RA was followed by a decrease of the levels of these peptides. The same pattern was observed in LS+Los rats, but the decrease in renal ANG II levels was much more pronounced in LS+Los rats than in NS+Los rats. Our results suggest that the increase in renal ANG II levels after salt restriction results mainly from an uptake of ANG II, via AT(1) receptors. Such elevated intrarenal ANG II levels could contribute to maintain sodium and fluid balance and arterial blood pressure during salt-deficiency states.

Collectrin and ACE2 in renal and intestinal amino acid transport

“…75 The resulting levels of Ang II are up to a 100 times higher than in plasma, which argues in favor of a local RAS as these levels cannot be achieved by the systemic supply alone. 76 Physiological actions of Ang II occur in the proximal tubule and further along the nephron in the distal segments and the collecting duct. 77 The Ang II locally produced favors Na + retention through the modulation of renal hemodynamics (decreased renal blood flow and glomerular filtration rate, afferent and efferent arteriole constriction and enhanced tubuloglomerular feedback) and increased Na + transport.…”

Review: Novel roles of intracrine angiotensin II and signalling mechanisms in kidney cells

“…[32][33][34]36,[86][87][88] Navar and associates were among the first to demonstrate that the kidney accumulated circulating Ang II when rats were infused with the exogenous peptide, 32,33,89 and their findings were later confirmed by many others. 34,36,88,90 Uptake of circulating or extracellular Ang II by the kidney appears to involve AT 1 -receptormediated internalisation, because AT 1 -receptor antagonists effectively prevent Ang II accumulation in this tissue (figure 2). 34,36,[87][88][89][90] While not internalised itself, the AT 2 -receptor may play a regulatory role in AT 1 -receptor-mediated internalisation of Ang II, since the AT 2 -receptor has been shown to antagonise most, if not all, of the known AT 1 -receptor mediated actions of Ang II.…”

Kidney-specific enhancement of ANG II stimulates endogenous intrarenal angiotensinogen in gene-targeted mice

“…The RAS has been acknowledged as an endocrine, paracrine, autocrine, and intracrine system and thus it has been difficult to delineate the quantitative contributions of systemically delivered vs. locally formed ANG peptides to the levels existing in any given tissue (37). In this regard, the kidneys are unique in terms of the tissue concentrations of ANG II, which are much greater than can be explained by the concentrations delivered by the arterial blood flow (19). There is substantial evidence that the major fraction of ANG II present in renal tissues is generated locally from angiotensinogen (AGT) delivered to the kidney as well as from AGT locally produced by proximal tubule cells (18).…”