Effects of changes in sodium balance on plasma and kidney angiotensin II levels in anesthetized and conscious Ren-2 transgenic rats
Abstract
Objective Since there is as yet no general agreement regarding the role of plasma and kidney angiotensin II (ANG II) in the development of hypertension in Ren-2 transgenic rats (TGR), in the present study we evaluated plasma and kidney ANG II levels in anesthetized and conscious TGR and in normotensive Hannover-Sprague-Dawley rats (HanSD) fed a normal salt diet (NS). Given the importance of ANG II in the development of salt-sensitive hypertension, and the fact that hypertensinogenic actions of ANG II are mediated via ANG II type 1 (AT,) receptors, the effects of high salt (HS) intake and of sodium depletion on blood pressure (1313), ANG II levels and kidney AT, receptor protein expression in TGR and HanSD were also examined.
Methods Rats were maintained on a NS diet (0.6% NaCl) or fed a HS diet (2% NaCl) for 4 days or were sodium depleted (40 mg/l furosemide for 1 day followed by 3 days of 0.01% NaCl diet). They were sacrificed either by an overdose of anesthetic (thiopental sodium) or by decapitation (without anesthetic) and plasma and kidney ANG II levels were determined by radioimmunoassay during the prehypertensive (32 days old), the early (52 days) and the maintenance (90 days) phases of hypertension.
Total kidney AT, receptor protein levels were assessed by Western blot analysis. Results In anesthetized animals fed the NS diet, plasma ANG II levels were lower in 32-day-old TGR than in HanSD, but at 52 and 90 days of age no significant differences were noted.
ANG II concentrations in kidney tissue were similar in 32- and 90-day-old TGR and HanSD, but were higher in 52-day-old TGR than in HanSD. In contrast, in conscious animals immediately after decapitation, plasma and kidney ANG II levels were higher in TGR than in HanSD at all ages.
HS diet did not change BP but suppressed ANG II levels in HanSD at all ages. In contrast, HS diet increased BP but did not decrease plasma and kidney ANG II levels in TGR at all ages.
Sodium restriction did not alter BP and resulted in a marked increase in ANG II levels in HanSD, but caused a significant decrease in BP in TGR without altering plasma or tissue ANG II concentrations. There were no significant differences in renal AT, receptor protein expression between HanSD and TGR at any age of any of the experimental groups.
Conclusions 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 BID regulation in this model.