Isis Akemi Katayama

Salt-Induced Cardiac Hypertrophy and Interstitial Fibrosis Are Due to a Blood Pressure–Independent Mechanism in Wistar Rats

High salt intake is a known cardiovascular risk factor and is associated with cardiac alterations. To better understand this effect, male Wistar rats were fed a normal (NSD: 1.3% NaCl), high 4 (HSD4: 4%), or high 8 (HSD8: 8%) salt diet from weaning until 18 wk of age. The HSD8 group was subdivided into HSD8, HSD8+HZ (15 mg . kg(-1) . d(-1) hydralazine in the drinking water), and HSD8+LOS (20 mg . kg(-1) . d(-1) losartan in the drinking water) groups. The cardiomyocyte diameter was greater in the HSD4 and HSD8 groups than in the HSD8+LOS and NSD groups. Interstitial fibrosis was greater in the HSD4 and HSD8 groups than in the HSD8+HZ and NSD groups. Hydralazine prevented high blood pressure (BP) and fibrosis, but not cardiomyocyte hypertrophy. Losartan prevented high BP and cardiomyocyte hypertrophy, but not fibrosis. Angiotensin II type 1 receptor (AT(1)) protein expression in both ventricles was greater in the HSD8 group than in the NSD group. Losartan, but not hydralazine, prevented this effect. Compared with the NSD group, the binding of an AT(1) conformation-specific antibody that recognizes the activated form of the receptor was lower in both ventricles in all other groups. Losartan further lowered the binding of the anti-AT(1) antibody in both ventricles compared with all other experimental groups. Angiotensin II was greater in both ventricles in all groups compared with the NSD group. Myocardial structural alterations in response to HSD are independent of the effect on BP. Salt-induced cardiomyocyte hypertrophy and interstitial fibrosis possibly are due to different mechanisms. Evidence from the present study suggests that salt-induced AT(1) receptor internalization is probably due to angiotensin II binding.

Inhalation of fine particulate matter during pregnancy increased IL-4 cytokine levels in the fetal portion of the placenta.

This study aimed to verify the development of placental and systemic inflammation in rats exposed to fine particulate matter before or during pregnancy. Wistar rats were exposed to filtered air (control) or to a load of 600 μg/m(3) of fine particles in the air. The gene expression of IL-1β, IL-4, IL-6, IL-10, INF-γ, TNF-α and Toll-like receptor 4 in the placenta was evaluated. The serum and placental concentrations of IL-1β, IL-4, IL-6, IL-10, INF-γ and TNF-α were measured. The total and differential blood leukocyte and blood platelet count was assessed. Compared to control animals, IL-4 content was elevated in the fetal portion of the placenta in rats exposed to air pollution before and during pregnancy. Increased IL-4 suggests that a placental inflammatory reaction may have occurred in response to exposure to fine particulate matter and that this cytokine was responsible, among possibly others factors, for resolution of the inflammatory reaction.

High-Salt Intake Induces Cardiomyocyte Hypertrophy in Rats in Response to Local Angiotensin II Type 1 Receptor Activation

Many studies have shown that risk factors that are independent of blood pressure (BP) can contribute to the development of cardiac hypertrophy (CH). Among these factors, high-salt (HS) intake was prominent. Although some studies have attempted to elucidate the role of salt in the development of this disease, the mechanisms by which salt acts are not yet fully understood. Thus, the aim of this study was to better understand the mechanisms of CH and interstitial fibrosis (IF) caused by HS intake. Male Wistar rats were divided into 5 groups according to diet [normal salt (NS; 1.27% NaCl) or HS (8% NaCl)] and treatment [losartan (LOS) (HS+LOS group), hydralazine (HZ) (HS+HZ group), or N-acetylcysteine (NAC) (HS+NAC group)], which was given in the drinking water. Tail-cuff BP, transverse diameter of the cardiomyocyte, IF, angiotensin II type 1 receptor (AT1) gene and protein expression, serum aldosterone, cardiac angiotensin II, cardiac thiobarbituric acid-reactive substances, and binding of conformation-specific anti-AT1 and anti-angiotensin II type 2 receptor (AT2) antibodies in the 2 ventricles were measured. Based on the left ventricle transverse diameter data, the primary finding was the occurrence of significant BP-independent CH in the HS+HZ group (96% of the HS group) and a partial or total prevention of such hypertrophy via treatment with NAC or LOS (81% and 67% of the HS group, respectively). The significant total or partial prevention of IF using all 3 treatments (HS+HZ, 27%; HS+LOS, 27%; and HS+NAC, 58% of the HS group, respectively), and an increase in the AT1 gene and protein expression and activity in groups that developed CH, confirmed that CH occurred via the AT1 in this experimental model. Thus, this study unveiled some relevant previously unknown mechanisms of CH induced by chronic HS intake in Wistar rats. The link of oxidative stress with CH in our experimental model is very interesting and stimulates further evaluation for its full comprehension.

1049 HIGH SALT INTAKE: EFFECT ON THE MYOCARDIAL STRUCTURE IS BLOOD PRESSURE INDEPENDENT

Objective: To evaluate the mechanisms of left (LV) and right (RV) ventricular hypertrophy induced by high salt intake. Methods: 18-week-old male Wistar rats were fed normal (NS: 1.3% NaCl) or high (HS 8%) salt diet since weaning. From the 7th week of age, two HS subgroups received hydralazine or losartan (HZ 15 or LO 20 mg/kg/day). Tail blood pressure (BP), cardiac mass to tibial length ratio (CM/TL), cardiomyocyte transverse diameter (TD), interstitial fibrosis (IF) and serum aldosterone (SA) were measured. Results (mean ± SEM – p < 0.05, n=8/group): At 18th week of age, BP (mmHg) was higher in HS (142 ± 6) than in NS (112 ± 2). BP in HS+HZ (116 ± 6) and HS+LO (118 ± 2) did not differ from NS. TD (&mgr;m) in the LV was higher in HS (19 ± 0.6) and HS+HZ (17 ± 0.8) than in NS (13 ± 0.4) and HS+LO (13 ± 0.8). TD in the RV was higher in HS (16 ± 0.3) and HS+HZ (14 ± 0.4) than in NS (12 ± 0.2) and HS+LO (12 ± 0.8). IF (%) was higher in HS than NS, HS+HZ and HS+LO in both ventricles (LV: HS 0.56 ± 0.08, NS 0.22 ± 0.04, HS+HZ 0.10 ± 0.04 and HS+LO 0.16 ± 0.03) (RV: HS 0.92 ± 0.06, NS 0.32 ± 0.02, HS+HZ 0.52 ± 0.08 and HS+LO 0.56 ± 0.08). CM/TL did not differ among all experimental groups. SA was lower in all groups that received salt overload than NS. Conclusions: In Wistar rats, salt induced cardiac hypertrophy is blood pressure independent and unrelated to changes in ventricular mass. It can be speculated that this result is an angiotensin II type 1 receptor-dependent mechanism. Supported by FAPESP and CNPq.