Conjugated equine estrogens and estradiol benzoate differentially modulate the natriuretic peptide system in spontaneously hypertensive rats.

OBJECTIVE: The purpose of this study was to compare the effects of conjugated equine estrogens (CEE) and estradiol benzoate on the blood pressure and body weight of spontaneously hypertensive rats (SHRs) and the associated changes in several components of the natriuretic peptide system. METHODS: The blood pressure of randomly distributed female SHRs and Wistar rats was determined by tail plethysmography. The rats were ovariectomized and, after 3 weeks, injected daily for 4 days with estradiol benzoate (5 µg/100 g/d), CEE (50 µg/100 g/d), or vehicle (corn oil 0.1 mL/100 g/d). One day after the last injection, the rats were decapitated, and their blood was collected to measure atrial natriuretic peptide (ANP) and estradiol. The atria were removed to measure ANP levels using radioimmunoassay and to quantify ANP messenger RNA expression using real-time polymerase chain reaction. The kidneys and adipose tissue were removed to analyze the expression of natriuretic peptide clearance receptor messenger RNA. RESULTS: A reduction in blood pressure was observed in estradiol-treated SHRs, but CEE treatment had no effect. Estradiol decreased the body weight and parametrial adipose tissue mass of SHRs. Estradiol-induced alterations in SHRs were accompanied by increased synthesis and release of ANP. CEE had no effect on body weight but increased the mesenteric adipose tissue mass of SHRs. CONCLUSIONS: These results indicate that estradiol and CEE have different effects on the reduction in body weight and blood pressure. These results are correlated with changes in plasma ANP levels.

Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha.

Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the effects of tibolone on the natriuretic peptide system have not been determined. We investigated the effects of tibolone on the natriuretic peptide system and pro-inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided into four groups: SHAM, OVX, OVX treated with 17ß-estradiol (OVX+E: 14 days) and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after ovariectomy. On day 35, blood was collected to determine atrial natriuretic peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, tissues were collected for determining ANP, natriuretic peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by RT-PCR. The cytokine levels of both IL-6 and TNF-α were increased in OVX animals. In comparison, IL-6 and TNF-α levels were reduced in OVX+E animals. TNF-α levels were reduced similarly in OVX+T animals, but IL-6 levels remained elevated in this group. The concentrations of ANP in the left atrium tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene expression in the kidney tissue was observed among the groups. Tibolone and 17ß-estradiol effectively increased plasma ANP and ANP mRNA levels in the left atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone normalizes plasma ANP and serum TNF-alpha levels our results suggest that treatment with tibolone has anti-inflammatory effects and could prevent cardiovascular disease in the long-term.

Natriuretic peptide system: a link between fat mass and cardiac hypertrophy and hypertension in fat-fed female rats.

The present study was designed to develop an animal model of hypertension and cardiac hypertrophy associated with obesity in female rats. Furthermore, we studied the involvement of the natriuretic peptide system in the mechanisms of these conditions. Obesity was induced in Wistar rats by a high fat diet and ovariectomy. The rats were divided into four groups: ovariectomized or sham-operated with high-fat diet and ovariectomized or sham-operated with control diet. After 24 weeks of diet, rats were killed, and their tissues were removed. Cardiac atrial natriuretic peptide (ANP), clearance receptor (NPr-C) gene expression was determined by PCR. ANP concentrations were measured in plasma. Ovariectomized fat-fed rats (OF) showed increased body weight, visceral fat depot and blood pressure and decreased sodium excretion compared to other groups. Also, these rats showed higher heart-to-body weight and cell diameters of ventricular cardiomyocytes and lower cardiac ANP mRNA and plasma ANP than the control group. The adipocyte and renal NPr-C mRNA of OF rats were higher than the control group. These data showed that combined ovariectomy and high fat diet elicited obesity, hypertension and cardiac hypertrophy. These results suggest that the impairment of the natriuretic peptide system may be one of the mechanisms involved not only in development of hypertension but also in cardiac hypertrophy associated with obesity in ovariectomized rats.