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Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension.
Hypertension. 2013 Feb; 61(2):417-24.H

Abstract

We examined the antihypertensive effects of valsartan, aliskiren, or both drugs combined on circulating, cardiac, and renal components of the renin-angiotensin system in congenic mRen2.Lewis hypertensive rats assigned to: vehicle (n=9), valsartan (via drinking water, 30 mg/kg per day; n=10), aliskiren (SC by osmotic mini-pumps, 50 mg/kg per day; n=10), or valsartan (30 mg/kg per day) combined with aliskiren (50 mg/kg per day; n=10). Arterial pressure and heart rate were measured by telemetry before and during 2 weeks of treatment; trunk blood, heart, urine, and kidneys were collected for measures of renin-angiotensin system components. Arterial pressure and left-ventricular weight/tibia length ratio were reduced by monotherapy of valsartan, aliskiren, and further reduced by the combination therapy. Urinary protein excretion was reduced by valsartan and further reduced by the combination. The increases in plasma angiotensin (Ang) II induced by valsartan were reversed by the treatment of aliskiren and partially suppressed by the combination. The decreases in plasma Ang-(1-7) induced by aliskiren recovered in the combination group. Kidney Ang-(1-12) was increased by the combination therapy whereas the increases in urinary creatinine mediated by valsartan were reversed by addition of aliskiren. The antihypertensive and antiproteinuric actions of the combined therapy were associated with marked worsening of renal parenchymal disease and increased peritubular fibrosis. The data show that despite improvements in the surrogate end points of blood pressure, ventricular mass, and proteinuria, dual blockade of Ang II receptors and renin activity is accompanied by worsening of renal parenchymal disease reflecting a renal homeostatic stress response attributable to loss of tubuloglomerular feedback by Ang II.

Authors+Show Affiliations

Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA. nmoniwa@wakehealth.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23232645

Citation

Moniwa, Norihito, et al. "Hemodynamic and Hormonal Changes to Dual Renin-angiotensin System Inhibition in Experimental Hypertension." Hypertension (Dallas, Tex. : 1979), vol. 61, no. 2, 2013, pp. 417-24.
Moniwa N, Varagic J, Ahmad S, et al. Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension. Hypertension. 2013;61(2):417-24.
Moniwa, N., Varagic, J., Ahmad, S., VonCannon, J. L., Simington, S. W., Wang, H., Groban, L., Brosnihan, K. B., Nagata, S., Kato, J., Kitamura, K., Gomez, R. A., Lopez, M. L., & Ferrario, C. M. (2013). Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension. Hypertension (Dallas, Tex. : 1979), 61(2), 417-24. https://doi.org/10.1161/HYPERTENSIONAHA.112.201889
Moniwa N, et al. Hemodynamic and Hormonal Changes to Dual Renin-angiotensin System Inhibition in Experimental Hypertension. Hypertension. 2013;61(2):417-24. PubMed PMID: 23232645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension. AU - Moniwa,Norihito, AU - Varagic,Jasmina, AU - Ahmad,Sarfaraz, AU - VonCannon,Jessica L, AU - Simington,Stephen W, AU - Wang,Hao, AU - Groban,Leanne, AU - Brosnihan,K Bridget, AU - Nagata,Sayaka, AU - Kato,Johji, AU - Kitamura,Kazuo, AU - Gomez,R Ariel, AU - Lopez,Maria L Sequeira, AU - Ferrario,Carlos M, Y1 - 2012/12/10/ PY - 2012/12/13/entrez PY - 2012/12/13/pubmed PY - 2013/3/21/medline SP - 417 EP - 24 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 61 IS - 2 N2 - We examined the antihypertensive effects of valsartan, aliskiren, or both drugs combined on circulating, cardiac, and renal components of the renin-angiotensin system in congenic mRen2.Lewis hypertensive rats assigned to: vehicle (n=9), valsartan (via drinking water, 30 mg/kg per day; n=10), aliskiren (SC by osmotic mini-pumps, 50 mg/kg per day; n=10), or valsartan (30 mg/kg per day) combined with aliskiren (50 mg/kg per day; n=10). Arterial pressure and heart rate were measured by telemetry before and during 2 weeks of treatment; trunk blood, heart, urine, and kidneys were collected for measures of renin-angiotensin system components. Arterial pressure and left-ventricular weight/tibia length ratio were reduced by monotherapy of valsartan, aliskiren, and further reduced by the combination therapy. Urinary protein excretion was reduced by valsartan and further reduced by the combination. The increases in plasma angiotensin (Ang) II induced by valsartan were reversed by the treatment of aliskiren and partially suppressed by the combination. The decreases in plasma Ang-(1-7) induced by aliskiren recovered in the combination group. Kidney Ang-(1-12) was increased by the combination therapy whereas the increases in urinary creatinine mediated by valsartan were reversed by addition of aliskiren. The antihypertensive and antiproteinuric actions of the combined therapy were associated with marked worsening of renal parenchymal disease and increased peritubular fibrosis. The data show that despite improvements in the surrogate end points of blood pressure, ventricular mass, and proteinuria, dual blockade of Ang II receptors and renin activity is accompanied by worsening of renal parenchymal disease reflecting a renal homeostatic stress response attributable to loss of tubuloglomerular feedback by Ang II. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/23232645/Hemodynamic_and_hormonal_changes_to_dual_renin_angiotensin_system_inhibition_in_experimental_hypertension_ L2 - https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.112.201889?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -