Restoration of endothelial function via enhanced nitric oxide synthesis after long-term treatment of raloxifene in adult hypertensive rats.
Arzneimittelforschung
; 55(2): 86-92, 2005.
Article
em En
| MEDLINE
| ID: mdl-15787275
ABSTRACT
Raloxifene (CAS 84449-90-1, RAL), a selective estrogen receptor modulator (SERM) effective for the prevention of post-menopausal osteoporosis, also has been shown to acutely stimulate nitric oxide (NO) synthesis associated with improved endothelium-dependent relaxation. The effect of a 3-month RAL treatment (10 mg/kg/d) on basal blood pressure, measured via the carotid artery, and its challenge with increasing doses of intravenous bradykinin (1, 3 and 10 nmol/kg) was investigated. Furthermore, aortic NO bioavailability and relaxation in 9-month-old male and female ovarectomized (OVX) spontaneously hypertensive rats (SHR) was tested. Calcium ionophore stimulated NO release from aortic endothelial cells and aortic superoxide (O2-) production was directly assessed by using electrochemical nanosensors. Relaxation studies were performed with acetylcholine (10(-8) to 10(-5) mol/L) following precontraction with phenylephrine (10(-7) mmol/L). Whereas basal blood pressure (BP) was not significantly decreased in RAL treated SHR, the dose-dependent challenge with bradykinin induced an enhanced BP reduction in either gender. In contrast to female animals, aortic segments from RAL treated male animals showed significantly improved relaxaSHR) to 360 +/- 15 nmol/L. Vice versa, O2- was decreased from 110 +/- 15 to 22 +/- 1 nmol/L. In female SHR, ovarectomy led to an increase/decrease of NO/O2- from 130 +/- 5 to 180 +/- 10 nmol/L and 82 +/- 7 to 68 +/- 3 nmol/L, respectively. These effects were significantly amplified by RAL treatment (NO 370 +/- 10 and O2- 25 +/- 2 nmol/L). The results show that long-term treatment with RAL has beneficial affects on the cardiovascular system in old male and female OVX SHR via an increased NO bioavailability.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Cloridrato de Raloxifeno
/
Moduladores Seletivos de Receptor Estrogênico
/
Hipertensão
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Arzneimittelforschung
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha