Inappropriately high circulating and intrarenal angiotensin II levels during dietary salt loading exacerbate hypertension in Cyp1a1–Ren-2 transgenic rats

2010 ◽  
Vol 28 (3) ◽  
pp. 495-509 ◽  
Author(s):  
Zuzana Husková ◽  
Zdeňka Vaňourková ◽  
Michaela Erbanová ◽  
Monika Thumová ◽  
Martin Opočenský ◽  
...  
2007 ◽  
Vol 30 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Zuzana Husková ◽  
Herbert J. Kramer ◽  
Zdenka Vaňourková ◽  
Monika Thumová ◽  
Jan Malý ◽  
...  

2018 ◽  
Vol 132 (2) ◽  
pp. 285-294 ◽  
Author(s):  
Alison H.M. Taylor ◽  
Alastair J. Rankin ◽  
Emily P. McQuarrie ◽  
E. Marie Freel ◽  
Natalie Z.M. Homer ◽  
...  

Background: Hypertension is prevalent in chronic kidney disease (CKD). Studies suggest that reduction in dietary salt intake reduces blood pressure (BP). We studied relationships between salt intake, BP and renin–angiotensin system regulation in order to establish if it is disordered in CKD. Methods: Mechanistic crossover study of CKD patients versus non-CKD controls. Participants underwent modified saline suppression test prior to randomization to either low or high salt diet for 5 days and then crossed over to the alternate diet. Angiotensin-II stimulation testing was performed in both salt states. BP, urea and electrolytes, and plasma aldosterone concentration (PAC) were measured. Results: Twenty-seven subjects were recruited (12 CKD, 15 control). There was no difference in age and baseline BP between the groups. Following administration of intravenous saline, systolic BP increased in CKD but not controls (131 ± 16 to 139 ± 14 mmHg, P=0.016 vs 125 ± 20 to 128 ± 22 mmHg, P=0.38). Median PAC reduced from 184 (124,340) to 95 (80,167) pmol in controls (P=0.003), but failed to suppress in CKD (230 (137,334) to 222 (147,326) pmol (P=0.17)). Following dietary salt modification, there was no change in BP in either group. Median PAC was lower following high salt compared with low salt diet in CKD and controls. There was a comparable increase in systolic BP in response to angiotensin-II in both groups. Discussion: We demonstrate dysregulation of aldosterone in CKD in response to salt loading with intravenous saline, but not to dietary salt modification.


2012 ◽  
Vol 13 (3) ◽  
pp. 360-366 ◽  
Author(s):  
Pieter M Jansen ◽  
Johannes Hofland ◽  
Anton H van den Meiracker ◽  
Frank H de Jong ◽  
AH Jan Danser

Introduction: Transgenic rats expressing the human (pro)renin receptor (h(P)RR) have elevated plasma aldosterone levels despite unaltered levels, in plasma and adrenal, of renin and angiotensin II. Materials and methods: To investigate whether renin/prorenin–(P)RR interaction underlies these elevated aldosterone levels, the effect of (pro)renin on steroidogenesis was compared with that of angiotensin II in two (P)RR-expressing human adrenocortical cell lines, H295R and HAC15. Angiotensin II rapidly induced extracellular signal-regulated kinase (ERK) phosphorylation and increased the expression of STAR, CYP21A2, CYP11B2, and CYP17A1 at 6 and 24 hours, whereas the expression of CYP11A1 and HSD3B2 remained unaltered. Incubation with renin or prorenin at nanomolar concentrations had no effect on the expression of any of the steroidogenic enzymes tested, nor resulted in ERK phosphorylation. Angiotensin II, but not renin or prorenin, induced aldosterone production. Conclusion: Although the (P)RR is present in adrenocortical cells, renin and prorenin do not elicit ERK phosphorylation nor directly affect steroid production via this receptor at nanomolar concentrations. Thus, direct (pro)renin–(P)RR interaction is unlikely to contribute to the elevated aldosterone levels in human (P)RR transgenic rats. This conclusion also implies that the aldosterone rise that often occurs during prolonged renin–angiotensin system blockade is rather due to the angiotensin II ‘escape’ during such blockade.


2009 ◽  
Vol 204 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Akiko Katoh ◽  
Hiroaki Fujihara ◽  
Toyoaki Ohbuchi ◽  
Tatsushi Onaka ◽  
W Scott Young ◽  
...  

We have generated rats bearing an oxytocin (OXT)-enhanced cyan fluorescent protein (eCFP) fusion transgene designed from a murine construct previously shown to be faithfully expressed in transgenic mice. In situ hybridisation histochemistry revealed that the Oxt–eCfp fusion gene was expressed in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) in these rats. The fluorescence emanating from eCFP was observed only in the SON, the PVN, the internal layer of the median eminence and the posterior pituitary (PP). In in vitro preparations, freshly dissociated cells from the SON and axon terminals showed clear eCFP fluorescence. Immunohistochemistry for OXT and arginine vasopressin (AVP) revealed that the eCFP fluorescence co-localises with OXT immunofluorescence, but not with AVP immunofluorescence in the SON and the PVN. Although the expression levels of the Oxt–eCfp fusion gene in the SON and the PVN showed a wide range of variations in transgenic rats, eCFP fluorescence was markedly increased in the SON and the PVN, but decreased in the PP after chronic salt loading. The expression of the Oxt gene was significantly increased in the SON and the PVN after chronic salt loading in both non-transgenic and transgenic rats. Compared with wild-type animals, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration and OXT and AVP levels, suggesting that the fusion gene expression did not disturb any physiological processes. These results suggest that our new transgenic rats are a valuable new tool to identify OXT-producing neurones and their terminals.


2007 ◽  
Vol 292 (2) ◽  
pp. H814-H819 ◽  
Author(s):  
Luis C. Matavelli ◽  
Xiaoyan Zhou ◽  
Jasmina Varagic ◽  
Dinko Susic ◽  
Edward D. Frohlich

We have previously shown that salt excess has adverse cardiac effects in spontaneously hypertensive rats (SHR), independent of its increased arterial pressure; however, the renal effects have not been reported. In the present study we evaluated the role of three levels of salt loading in SHR on renal function, systemic and renal hemodynamics, and glomerular dynamics. At 8 wk of age, rats were given a 4% ( n = 11), 6% ( n = 9), or 8% ( n = 11) salt-load diet for the ensuing 8 wk; control rats ( n = 11) received standard chow (0.6% NaCl). Rats had weekly 24-h proteinuria and albuminuria quantified. At the end of salt loading, all rats had systemic and renal hemodynamics measured; glomerular dynamics were specially studied by renal micropuncture in the control, 4% and 6% salt-loaded rats. Proteinuria and albuminuria progressively increased by the second week of salt loading in the 6% and 8% salt-loaded rats. Mean arterial pressure increased minimally, and glomerular filtration rate decreased in all salt-loaded rats. The 6% and 8% salt-loaded rats demonstrated decreased renal plasma flow and increased renal vascular resistance and serum creatinine concentration. Furthermore, 4% and 6% salt-loaded rats had diminished single-nephron plasma flow and increased afferent and efferent arteriolar resistances; glomerular hydrostatic pressure also increased in the 6% salt-loaded rats. In conclusion, dietary salt loading as low as 4% dramatically deteriorated renal function, renal hemodynamics, and glomerular dynamics in SHR independent of a minimal further increase in arterial pressure. These findings support the concept of a strong independent causal relationship between salt excess and cardiovascular and renal injury.


1999 ◽  
Vol 104 (6) ◽  
pp. 751-760 ◽  
Author(s):  
Vijaykumar R. Holla ◽  
Keiko Makita ◽  
Peter G. Zaphiropoulos ◽  
Jorge H. Capdevila

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Fiona Dianne McBryde ◽  
Carolyn J Barrett ◽  
Sarah‐Jane Guild ◽  
Simon C Malpas

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