Differential Regulation of Angiotensin Peptides in Plasma and Kidney: Effects of Adrenalectomy and Estrogen Treatment

Abstract

Eight angiotensin peptides [angiotensin-(1-7), angiotensin II, angiotensin-(1-9), angiotensin I, angiotensin-(2-7), angiotensin-(2-8), angiotensin-(2-9), and angiotensin-(2-10)] were measured in plasma and kidney of adrenalectomized rats and estrogen-treated rats. In comparison with sham-operated rats, adrenalectomy increased plasma renin levels by 50-fold and reduced plasma angiotensinogen levels by 67%. Adrenalectomy increased plasma angiotensin peptide levels by 9- to 30-fold, but the increases in renal angiotensin peptide levels were much less than those seen for plasma. In comparison with vehicle-treated rats, estrogen treatment increased plasma angiotensinogen levels by 3-fold and reduced plasma renin levels by 41%. Estrogen treatment decreased plasma angiotensin peptide levels, whereas renal angiotensin peptide levels increased by as much as 2- to 3-fold. These results confirm the differential regulation of angiotensin peptide levels in plasma and kidney, and provide further support for the essential role of angiotensinogen in modulating plasma and tissue angiotensin peptide levels.

Enhanced expression of Ang-(1-7) during pregnancy

“…Prominent antihypertensive effects of Ang-(1-7) were demonstrated in experimental hypertensive models (32,33). Local regional angiotensin peptide levels (kidney and adrenal) are modulated by the estrous cycle, resulting in an increase in Ang I and/or its product Ang-(1-7) during estrus (34,35).…”

Combined Blockade of the Renin-Angiotensin System With Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Type 1 Receptor Antagonists

“…Apart from age, individual susceptibility, genetic factors, implication of multiple biological pathogenic factors, and the lag time between proteinuria appearance and treatment initiation, this insufficient response may be explained by incomplete blockade of the RAS, 51 especially if intrarenal RAS is regulated independently of circulating RAS. 52 The huge amount of renin synthesized and released locally, the limited amount of renal endothelial ACE, 53 the compartmentalization of Ang II in interstitial and tubular fluids, 54 the intrarenal consumption of angiotensinogen, 52 and the uptake of Ang II by the renal AT1Rs 55 influences the intrarenal levels of Ang I and Ang II, which differ from their plasma levels. By increasing and prolonging intrarenal Ang II neutralization, specific renal benefits are expected from the combined blockade in renal tissue under pathological circumstances, but adverse renal effects may also be expected as a consequence of renal hypoperfusion and vasodilatation under certain circumstances.…”

Influence of the M235T Polymorphism of Human Angiotensinogen (AGT) on Plasma AGT and Renin Concentrations after Ethinylestradiol Administration1

“…Actually, EE administration reduced, although not significantly, plasma active renin concentrations from day 1 to day 7. Partial suppression of renin release and synthesis, as a consequence of high concentrations of renin substrate during the administration of synthetic estrogens, has been previously reported in rat models (8,23) and in humans (3). It has also been reported during the oral administration of natural estrogens in postmenopausal women (24).…”

“…The similarity in plasma Ang I and Ang II concentrations, observed in both groups, was attributable to a decrease in renin release after sodium depletion and angiotensin-converting enzyme (ACE) inhibition in the EE group, even though the in vitro Ang I production rate (PRA/active renin ratio) was significantly higher in the EE group than in the placebo group. The decrease in renin release after furosemide and ACE inhibition after EE administration was probably caused by the inhibition of renin release by high local Ang II concentrations at the level of the juxtaglomerular cells in the presence of an increase in AGT (23). Actually, EE administration reduced, although not significantly, plasma active renin concentrations from day 1 to day 7.…”

“…It is difficult to extrapolate these results to estrogeninduced hypertension or pregnancy-induced hypertension because: 1) our study was restricted to male subjects who were given EE during a short period of time; and 2) the consequences of EE administration were only assessed on the circulating RAS. Campbell et al (23) found that the administration of synthetic estrogens to rats induces an increase in the concentration of angiotensin peptides in the kidney, whereas a decrease is observed in plasma. It is therefore possible to observe no change in the equilibrium of the circulating RAS despite an increase in angiotensin production in the kidney.…”