Effects of changes in sodium balance on plasma and kidney angiotensin II levels in anesthetized and conscious Ren-2 transgenic rats

Abstract

On the basis of our present results we conclude that TGR exhibit a disrupted interaction between sodium homeostasis and the regulation of the renin-angiotensin system (RAS) activity which results in the loss of BP regulation in this model.

Long-Term Prevention of Hypertension and End-Organ Damage in Ren-2 Transgenic Rats Is Achieved Only with Persistent but Not Transient AT₁Receptor Blockade

“…Conflicting data concerning ANG II concentrations in TGR were reported, showing either similar [8] or higher [31,32] plasma concentrations. The finding of similar concentrations of ANG II in anesthetized TGR and HanSD rats in the present study are fully in accordance with our previous study showing strong differences in plasma and kidney concentrations of ANG II between conscious and anesthetized animals [33] . Finally, the increased plasma and decreased kidney ANG II levels in TGR continuously treated with candesartan show that candesartan is an effective antihypertensive agent resembling other AT 1 receptor antagonists [32] .…”

Effects of Dietary Salt Load and Salt Depletion on the Course of Hypertension and Angiotensin II Levels in Male and Female Heterozygous Ren-2 Transgenic Rats

“…On the other hand, there are studies that reported that plasma and tissue ANG II concentrations are significantly higher in hypertensive TGR than in normotensive HanSD rats [11][12][13][14][15][16] , suggesting that enhanced formation of ANG II is the main pathophysiological mechanism responsible for the development and maintenance of hypertension in this model. Whereas it is difficult to reconcile these contradictory results, we found in our recent study [17] first that anesthesia increases plasma and kidney ANG II levels in HanSD rats to a greater extent than in TGR and second that in conscious rats, i.e. when samples were harvested immediately after decapitation, plasma and tissue ANG II concentrations in male heterozygous TGR were higher than in HanSD rats.…”

“…when samples were harvested immediately after decapitation, plasma and tissue ANG II concentrations in male heterozygous TGR were higher than in HanSD rats. In addition, we found that male TGR display a lack of appropriate responses of plasma and kidney ANG II levels to changes in salt balance [17] . Moreover, we have recently found that other ANG II-dependent rat models such as 2-kidney, 1-clip Goldblatt and ANG II-infused hypertensive rats responded to anesthesia by markedly lower increases in plasma and kidney ANG II levels than normotensive rats [18] .…”

“…Since an emerging body of evidence indicates that TGR exhibit a salt-sensitive component of hypertension [27][28][29][30] , and since we have recently demonstrated that this salt sensitivity in male heterozygous TGR is associated with a loss of the normal regulatory effect of changes in dietary salt intake on ANG II production [17] , the second aim of the present study was to delineate the effects of oral salt loading and salt depletion on BP and plasma and kidney ANG II levels in female heterozygous TGR and age-matched female HanSD rats and to compare these responses to changes in sodium balance with those in male TGR and HanSD rats.…”

“…0.01 g NaCl/100 g rat chow; Altromin, Lage, Germany) before the experiment. Previous studies have demonstrated that this type of salt depletion leads to potent stimulation of the RAS [17,[31][32][33] . The rats were allowed free access to food and tap water until the day of the experiment.…”