| Hemodynamic and hormonal changes to dual renin-angiotensin system inhibition in experimental hypertension. | |
| | |
MedLine Citation:
|
PMID: 23232645 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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:
|
Norihito Moniwa; Jasmina Varagic; Sarfaraz Ahmad; Jessica L VonCannon; Stephen W Simington; Hao Wang; Leanne Groban; K Bridget Brosnihan; Sayaka Nagata; Johji Kato; Kazuo Kitamura; R Ariel Gomez; Maria L Sequeira Lopez; Carlos M Ferrario |
Related Documents
:
|
7205365 - Measurement of ventricular function by ecg gating during atrial fibrillation. 17817815 - Heart activity and high-pressure circulation in cirripedia. 7871245 - Rate of discharge and morphology of sweat glands in the perineal, lumbodorsal and scrot... 1178325 - Note on relation of autonomic perception to voluntary control of heart rate. 2688285 - Brain hypoperfusion post-resuscitation. 9495625 - Remodelling of conduit arteries in hypertension: special emphasis on the mechanical and... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-12-10 |
Journal Detail:
|
Title: Hypertension Volume: 61 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2013 Feb |
Date Detail:
|
Created Date: 2013-01-17 Completed Date: 2013-03-20 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 417-24 Citation Subset: IM |
Affiliation:
|
Division of Surgical Sciences, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA. nmoniwa@wakehealth.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amides
/
pharmacology*,
therapeutic use Angiotensin II / blood Angiotensin II Type 1 Receptor Blockers / pharmacology*, therapeutic use Animals Antihypertensive Agents / pharmacology*, therapeutic use Blood Pressure / drug effects, physiology Drug Therapy, Combination Fumarates / pharmacology*, therapeutic use Heart Rate / drug effects, physiology Hemodynamics / drug effects, physiology Hypertension / blood, drug therapy*, physiopathology Kidney / drug effects, metabolism Male Rats Renin / antagonists & inhibitors* Renin-Angiotensin System / drug effects*, physiology Telemetry Tetrazoles / pharmacology*, therapeutic use Valine / analogs & derivatives*, pharmacology, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
|
AG-033727/AG/NIA NIH HHS; HL-051952/HL/NHLBI NIH HHS; P01 HL051952/HL/NHLBI NIH HHS; R01 AG033727/AG/NIA NIH HHS; R01 DK091330/DK/NIDDK NIH HHS; R37 HL066242/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amides; 0/Angiotensin II Type 1 Receptor Blockers; 0/Antihypertensive Agents; 0/Fumarates; 0/Tetrazoles; 11128-99-7/Angiotensin II; 137862-53-4/valsartan; 502FWN4Q32/aliskiren; 7004-03-7/Valine; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score...
Next Document: Functional Cross-Talk Between Aldosterone and Angiotensin-(1-7) in Ventricular Myocytes.