Cardiac hypertrophy and cardiac renin–angiotensin system in Dahl rats on high salt intake

Introduction: Transgenic mice with transient cardiac expression of constitutively active Galpha q (Gαq-TG) caused progressive heart failure and ventricular arrhythmias after the initiating stimulus becomes undetectable. However, the mechanisms are still unknown. Renin-angiotensin system plays a critical role in the development of cardiac hypertrophy and heart failure. We examined the effects of chronic administration of olmesartan on ventricular function, the number of premature ventricular contractions (PVC), and ventricular remodeling in Gαq-TG mice. Methods and Results: Olmesartan (1 mg/kg/day) or vehicle was chronically administered to Gαq-TG from 6 to 32 weeks of age, and all experiments were performed in mice at the age of 32 weeks. Chronic olmesartan treatment prevented the severe reduction of left ventricular fractional shortening and inhibited ventricular interstitial fibrosis and ventricular myocyte hypertrophy in Gαq-TG. Electrocardiogram demonstrated that premature ventricular contraction (PVC) was frequently (more than 20 beats/min) observed in 9 of 10 vehicle-treated Gαq-TG but in none of 10 olmesartan -treated Gαq-TG. The QT interval was significantly shorter in olmesartan-treated Gαq-TG than vehicle-treated Gαq-TG. CTGF, collagen type 1, ANP, BNP, and β-MHC gene expression was increased in vehicle-treated Gαq-TG. Olmesartan significantly decreased these gene expressions in Gαq-TG. Moreover, protein expressions of canonical transient receptor potential (TRPC) channels 3 and 6 increased in vehicle-treated Gαq-TG hearts. Olmesartan significantly decreased TRPC6 expressions in Gαq-TG. Angiotensin converting enzyme (ACE) 1 and 2 gene expressions were also increased in vehicle-treated Gαq-TG and was not decreased to the control level in olmesartan-treated Gαq-TG. Conclusions: These findings suggest that renin-angiotensin system has an important role in the development of cardiac hypertrophy and heart failure even if the initiating stimulus is different from the activation of renin-angiotensin system.

Download Full-text

Brain Renin–Angiotensin System in Hypertension, Cardiac Hypertrophy, and Heart Failure

Frontiers in Physiology ◽

10.3389/fphys.2011.00115 ◽

2012 ◽

Vol 2 ◽

Cited By ~ 8

Author(s):

Luciana Aparecida Campos ◽

Michael Bader ◽

Ovidiu Constantin Baltatu

Keyword(s):

Heart Failure ◽

Cardiac Hypertrophy ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin

Download Full-text

Activation of the Renin-Angiotensin System Mediates the Effects of Dietary Salt Intake on Atherogenesis in the Apolipoprotein E Knockout Mouse

Hypertension ◽

10.1161/hypertensionaha.112.191767 ◽

2012 ◽

Vol 60 (1) ◽

pp. 98-105 ◽

Cited By ~ 35

Author(s):

Chris Tikellis ◽

Raelene J. Pickering ◽

Despina Tsorotes ◽

Olivier Huet ◽

Jaye Chin-Dusting ◽

...

Keyword(s):

Apolipoprotein E ◽

Knockout Mouse ◽

Salt Intake ◽

Renin Angiotensin System ◽

Dietary Salt ◽

Angiotensin System ◽

Renin Angiotensin ◽

Dietary Salt Intake

Download Full-text

Factors affecting Potassium Balance During Frusemide Administration

Clinical Science ◽

10.1042/cs0670195 ◽

1984 ◽

Vol 67 (2) ◽

pp. 195-203 ◽

Cited By ~ 26

Author(s):

Christopher S. Wilcox ◽

William E. Mitch ◽

Ralph A. Kelly ◽

Paul A. Friedman ◽

Paul F. Souney ◽

...

Keyword(s):

Salt Intake ◽

Normal Subjects ◽

Plasma Aldosterone ◽

High Salt ◽

Renin Angiotensin Aldosterone System ◽

Plasma Aldosterone Concentration ◽

Water Load ◽

Renin Angiotensin ◽

High Salt Intake ◽

Low Salt

1. We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and antidiuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given. 2. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral. 3. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (−86 ± 7 mmol/3 days; P < 0.001). 4. Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance. 5. When a water load was given concurrently with frusemide, the acute kaliuresis was >30% lower compared with that seen with frusemide alone, even though the natriuretic response was unchanged. 6. We conclude that: (a) K+ balance is maintained when frusemide is given during liberal Na+ intake because acute K+ losses are offset by subsequent renal K+ retention; (b) this compensatory K+ retention can be inhibited by aldosterone release which could account for the negative K+ balance seen during salt restriction; (c) the short-term kaliuretic response to frusemide is augmented by release of both ADH and aldosterone whereas changes in K+ balance over 3 days of frusemide are dependent on plasma aldosterone concentration.

Download Full-text