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Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats.
Am J Physiol Heart Circ Physiol. 2006 Nov; 291(5):H2166-72.AJ

Abstract

The generation of the Lew.Tg(mRen2) congenic hypertensive rat strain, developed through a backcross of the hypertensive (mRen2)27 transgenic rat with normotensive Lewis rats, provides a new model by which primary hypertension can be studied without the genetic variability found in the original strain. The purpose of this study was to characterize the Lew.Tg(mRen2) rats by dually investigating the effects of type 1 angiotensin II (ANG II) receptor (AT(1)) blockade and angiotensin-converting enzyme (ACE) activity inhibition on the ANG-(1-7)/ACE2 axis of the renin-angiotensin system in this new hypertensive model. The control of blood pressure elicited by 12-day administration of either lisinopril (mean difference change = 92 +/- 2, P < 0.05) or losartan (mean difference change = 69 +/- 2, P < 0.05) was associated with 54% and 33% increases in cardiac ACE2 mRNA and 54% and 43% increases in cardiac ACE mRNA, respectively. Lisinopril induced a 3.1-fold (P < 0.05) increase in renal cortical expression of ACE2, whereas losartan increased ACE2 mRNA 3.5-fold (P < 0.05). Both treatment regimens increased renal ACE mRNA 2.6-fold (P < 0.05). The two therapies augmented ACE2 protein activity, as well as increased cardiac and renal AT(1) receptor mRNAs. ACE inhibition reduced plasma ANG II levels (81%, P < 0.05) and increased plasma ANG-(1-7) (265%, P < 0.05), whereas losartan had no effect on the peptides. In contrast with what had been shown in normotensive rats, ACE inhibition decreased renal ANG II excretion and transiently decreased ANG-(1-7) excretion, whereas losartan treatment was associated with a consistent decrease in ANG-(1-7) urinary excretion rates. In response to the treatments, the expression of both renal cortical renin and angiotensinogen mRNAs was significantly augmented. The paradoxical effects of blockade of ANG II synthesis and activity on urinary excretion rates of the peptides and plasma angiotensins levels suggest that, in Lew.Tg(mRen2) congenic rats, a failure of compensatory ACE2 and ANG-(1-7)-dependent vasodepressor mechanisms may contribute both to the development and progression of hypertension driven by increased formation of endogenous ANG II.

Authors+Show Affiliations

Hypertension and Vascular Disease Center, Wake Forest Univ. School of Medicine, Winston-Salem, NC 27157, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16766648

Citation

Jessup, Jewell A., et al. "Effect of Angiotensin II Blockade On a New Congenic Model of Hypertension Derived From Transgenic Ren-2 Rats." American Journal of Physiology. Heart and Circulatory Physiology, vol. 291, no. 5, 2006, pp. H2166-72.
Jessup JA, Gallagher PE, Averill DB, et al. Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. Am J Physiol Heart Circ Physiol. 2006;291(5):H2166-72.
Jessup, J. A., Gallagher, P. E., Averill, D. B., Brosnihan, K. B., Tallant, E. A., Chappell, M. C., & Ferrario, C. M. (2006). Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. American Journal of Physiology. Heart and Circulatory Physiology, 291(5), H2166-72.
Jessup JA, et al. Effect of Angiotensin II Blockade On a New Congenic Model of Hypertension Derived From Transgenic Ren-2 Rats. Am J Physiol Heart Circ Physiol. 2006;291(5):H2166-72. PubMed PMID: 16766648.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of angiotensin II blockade on a new congenic model of hypertension derived from transgenic Ren-2 rats. AU - Jessup,Jewell A, AU - Gallagher,Patricia E, AU - Averill,David B, AU - Brosnihan,K Bridget, AU - Tallant,E Ann, AU - Chappell,Mark C, AU - Ferrario,Carlos M, Y1 - 2006/06/09/ PY - 2006/6/13/pubmed PY - 2007/1/16/medline PY - 2006/6/13/entrez SP - H2166 EP - 72 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 291 IS - 5 N2 - The generation of the Lew.Tg(mRen2) congenic hypertensive rat strain, developed through a backcross of the hypertensive (mRen2)27 transgenic rat with normotensive Lewis rats, provides a new model by which primary hypertension can be studied without the genetic variability found in the original strain. The purpose of this study was to characterize the Lew.Tg(mRen2) rats by dually investigating the effects of type 1 angiotensin II (ANG II) receptor (AT(1)) blockade and angiotensin-converting enzyme (ACE) activity inhibition on the ANG-(1-7)/ACE2 axis of the renin-angiotensin system in this new hypertensive model. The control of blood pressure elicited by 12-day administration of either lisinopril (mean difference change = 92 +/- 2, P < 0.05) or losartan (mean difference change = 69 +/- 2, P < 0.05) was associated with 54% and 33% increases in cardiac ACE2 mRNA and 54% and 43% increases in cardiac ACE mRNA, respectively. Lisinopril induced a 3.1-fold (P < 0.05) increase in renal cortical expression of ACE2, whereas losartan increased ACE2 mRNA 3.5-fold (P < 0.05). Both treatment regimens increased renal ACE mRNA 2.6-fold (P < 0.05). The two therapies augmented ACE2 protein activity, as well as increased cardiac and renal AT(1) receptor mRNAs. ACE inhibition reduced plasma ANG II levels (81%, P < 0.05) and increased plasma ANG-(1-7) (265%, P < 0.05), whereas losartan had no effect on the peptides. In contrast with what had been shown in normotensive rats, ACE inhibition decreased renal ANG II excretion and transiently decreased ANG-(1-7) excretion, whereas losartan treatment was associated with a consistent decrease in ANG-(1-7) urinary excretion rates. In response to the treatments, the expression of both renal cortical renin and angiotensinogen mRNAs was significantly augmented. The paradoxical effects of blockade of ANG II synthesis and activity on urinary excretion rates of the peptides and plasma angiotensins levels suggest that, in Lew.Tg(mRen2) congenic rats, a failure of compensatory ACE2 and ANG-(1-7)-dependent vasodepressor mechanisms may contribute both to the development and progression of hypertension driven by increased formation of endogenous ANG II. SN - 0363-6135 UR - https://www.unboundmedicine.com/medline/citation/16766648/Effect_of_angiotensin_II_blockade_on_a_new_congenic_model_of_hypertension_derived_from_transgenic_Ren_2_rats_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.00061.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -