Both central sympathoexcitation and peripheral angiotensin II-dependent vasoconstriction contribute to hypertension development in immature heterozygous Ren-2 transgenic rats

Author(s):  
Lenka Řezáčová ◽  
Ivana Vaněčková ◽  
Silvie Hojná ◽  
Anna Vavřínová ◽  
Pavol Valovič ◽  
...  
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.


2010 ◽  
Vol 28 (3) ◽  
pp. 495-509 ◽  
Author(s):  
Zuzana Husková ◽  
Zdeňka Vaňourková ◽  
Michaela Erbanová ◽  
Monika Thumová ◽  
Martin Opočenský ◽  
...  

Hypertension ◽  
2000 ◽  
Vol 35 (1) ◽  
pp. 360-366 ◽  
Author(s):  
Eero Mervaala ◽  
Dominik N. Müller ◽  
Joon-Keun Park ◽  
Ralph Dechend ◽  
Folke Schmidt ◽  
...  

2007 ◽  
Vol 30 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Zuzana Husková ◽  
Herbert J. Kramer ◽  
Zdenka Vaňourková ◽  
Monika Thumová ◽  
Jan Malý ◽  
...  

2007 ◽  
Vol 28 (11) ◽  
pp. 1737-1745 ◽  
Author(s):  
Xu-guang Li ◽  
Jiang-tao Yan ◽  
Xi-zheng Xu ◽  
Jia-ning Wang ◽  
Li-ming Cheng ◽  
...  

2004 ◽  
Vol 22 (4) ◽  
pp. 819-825 ◽  
Author(s):  
Libor Kopkan ◽  
Herbert J Kramer ◽  
Zuzana Husková ◽  
Zdeňka Vaňourková ◽  
Angela Bäcker ◽  
...  

1997 ◽  
Vol 240 (2) ◽  
pp. 367-371 ◽  
Author(s):  
Concepción Peiró ◽  
Javier Angulo ◽  
José Luis Llergo ◽  
Leocadio Rodrı&#x;guez-Mañas ◽  
Jesús Marı&#x;n ◽  
...  

1997 ◽  
Vol 272 (1) ◽  
pp. H493-H500 ◽  
Author(s):  
G. Noll ◽  
M. G. Lang ◽  
M. R. Tschudi ◽  
D. Ganten ◽  
T. F. Luscher

We investigated vascular function in mouse Ren-2 transgenic rats with hypertension. Mesenteric resistance arteries of transgenic and Sprague-Dawley rats (controls) were isolated at ages 6 and 12 wk and suspended in myographs for isometric tension recording. Systolic blood pressure was higher in transgenic than control rats (P < 0.05). Contractions to norepinephrine and endothelin-1 were comparable in transgenic and control rats, but the sensitivity decreased with age in both strains (P < 0.05). Contractions to angiotensin I were comparable in 6-wk-old transgenic rats and controls, but the response to angiotensin I was more pronounced in transgenic rats at 12 wk of age. Contractions to angiotensin II were higher in transgenic rats and decreased with age in both strains. Preincubation with the cyclooxygenase inhibitor meclofenamate or the thromboxane receptor antagonist SQ-30741 blunted the response only in 6-wk-old transgenic rats. In quiescent vascular rings, acetylcholine evoked endothelium-dependent contractions after inhibition of nitric oxide formation by N omega-nitro-L-arginine methyl ester only in transgenic rats. These contractions were inhibited by SQ-30741 (P < 0.05) but not by the thromboxane synthase inhibitor CGS-13080. Contractions to the thromboxane analogue U-46619 were comparable in both strains at the age of 6 wk; sensitivity was increased in transgenic rats at 12 wk (P < 0.05). In conclusion, in mesenteric resistance arteries of Ren-2 transgenic rats I) contractions to angiotensin I and II but not to norepinephrine and endothelin-1 are increased, and 2) acetylcholine as well as angiotensin II modulate endothelium-dependent contractions mediated by prostaglandin H2. These alterations together with increased sensitivity to thromboxane could contribute to maintenance as well as to impaired tissue perfusion of this form of hypertension.


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