Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

Maternal protein restriction may be a risk factor for cardiovascular disorders in adulthood. The RAS (renin-angiotensin-system) plays a pivotal role in cardiac remodeling. Components of the RAS, including angiotensin II (AngII) and its receptors type 1 (AT1R) and 2 (AT2R) are expressed in the heart. This study investigates whether gestational protein restriction alters the expression and localization of AT1R and AT2R and RAS signaling pathway proteins in parallel with left ventricle hypertrophy and systemic hypertension in male offspring. Dams were kept on normal (NP, 17% protein) or low (LP, 6% protein) protein diet during pregnancy. Systolic blood pressure (SBP) of male offspring was measured from the 8th to 16th week and left ventricles of 16-wk-old rats were processed for histology, morphometric, immunoblotting and immunohistochemistry. LP offspring showed a significant reduction in birth body weight and SBP increased significantly from the 8th week. Left ventricle mass and cardiomyocytes area were also significantly higher in LP animals. Widespread perivascular fibrosis was not detected in the heart tissue. Analysis by immunoblotting and immunohistochemistry demonstrated a significant enhance in cardiomyocyte expression of AT1R and ERK1 in LP offspring. Expression of PI3K in LP was significantly reduced in cardiomyocytes and in the intramural coronary wall, while AT2R expression was unchanged in the NP group. We also found reduced LP expression of JAK2 and STAT3. In conclusion, our data also suggest that changes in the RAS may play a role in the ventricular growth through upregulation of the AT1-mediated ERK1/2 response, despite unchanged AT2R expression.

Hypertrophic cardiomyopathy and left ventricular non-compaction:Distinct diseases or variant phenotypes of a single condition?

Hypertrophic cardiomyopathy(HCM)is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle(LV)wall that cannot be solely attributed to abnormal loading conditions.HCM may present with an intraventricular or LV outflow tract obstruction,diastolic dysfunction,myocardial fibrosis and/or ventricular arrhythmias.Differentiating HCM from other diseases associated with LV hypertrophy,such as hypertension,aortic stenosis,or LV non-compaction(LVNC),can at times be challenging.LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae,often accompanied by increased LV myocardial mass.Previous studies indicate that the LVNC phenotype may be observed in up to 5%of the general population;however,in most cases,it is a benign finding with no impact on clinical outcomes.Nevertheless,LVNC can occasionally lead to LV systolic dysfunction,manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy,with an increased risk of thrombus formation and arterial embolism.In extreme cases,where LVNC is associated with a very thickened LV wall,it can even mimic HCM.There is growing evidence of an overlap between HCM and LVNC,including similar genetic mutations and clinical presentations.This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are,in fact,two distinct entities.

Long-term effects of imidapril on calcium and potassium currents in rabbit left ventricular hypertrophic myocytes

Objective To investigate the long-term effects of imidapril (IMI) on action potential and calcium and potassium currents in rabbit left ventricular hypertrophic myocytes. Methods Rabbits were randomly divided into three groups: IMI-treated, hypertrophic and sham-operated control groups. Cardiac hypertrophy was induced in hypertrophy group by partial ligation of the abdominal aorta. In the IMI-treated group, the rabbits were administered IMI (1.5 mg·kg -1·d -1) for 8 weeks after surgery. In the sham-operated control group, the animals underwent an abdominal laparotomy without further procedure. Whole-cell patch clamp technique was used to record ionic currents. Results Membrane capacitance was larger in hypertrophic cells than in sham-operated cells or IMI-treated cells. Action potential duration was lengthened in hypertrophic cells and was remarkably shortened by IMI. The density of I Ca,L was reduced from 12.8±0.7 pA/pF in the sham-operated cells, to 7.7±0.8 pA/pF in hypertrophic cells, while it resembled the control cells after IMI treatment (11.9±1.0 pA/pF). After IMI treatment, the density of I Ks,tail was enhanced from 2.5±0.1 pA/pF in hypertrophic cells to 4.7±0.6 pA/pF (n=7, P<0.01), which was similar to the sham-operated cells. The densities of I to and I K1 were significantly increased in IMI-treated cells, from 3.8±0.4 pA/pF and 3.7±0.5 pA/pF in the hypertrophic cells to 6.4±0.8 pA/pF and 6.5±0.3 pA/pF, respectively, but the I Kr densities were not different in the three groups. Conclusion IMI could reverse the increase in membrane capacitance in hypertrophic cells, shorten action potential duration, and increase the densities of I Ca, L, I Ks, I to and I K1 in hypertrophic cells.