Elevated mean arterial pressure in the ovariectomized rat was normalized by ET(A) receptor antagonist therapy: absence of cardiac hypertrophy and fibrosis.
1. The influence of menopause on ventricular function and remodelling remains undefined. The following study examined the effect of ovariectomy on ventricular contractility, cardiac hypertrophy and extracellular matrix protein expression. 2. Elevated circulating levels of the vasoconstrictor endothelin-1 have been reported in post-menopausal women. Moreover, endothelin-1 has been shown to influence blood pressure, ventricular function and cardiac remodelling. In this regard, the potential pathophysiological role of endothelin-1 in the ovariectomized rat was assessed via the administration of the selective endothelin(A) receptor (ET(A)) antagonist BMS-182874. 3. In 3 and 6 week ovariectomized female Sprague - Dawley rats, uterus atrophy was associated with a significant increase in mean arterial pressure, and left ventricular systolic pressure, as compared to sham. By contrast, right ventricular contractile indices were normal in the ovariectomized rat. Despite increased systolic load, left ventricular hypertrophy was not evident, prepro-atrial natriuretic peptide (prepro-ANP) mRNA levels and collagen protein content were similar to sham. 4. The treatment of ovariectomized rats with BMS-182874 (60 mg kg(-1) per day) did not reverse uterus atrophy. However, BMS-182874 normalized mean arterial pressure, and left ventricular systolic pressure in the ovariectomized rat. 5. Thus, despite elevated blood pressure, ovariectomized rats were not associated with either cardiac hypertrophy or fibrosis. Lastly, endothelin-1, acting via the stimulation of the ET(A) receptor represents an integral mechanism implicated in the increase of mean arterial pressure following ovariectomy.
Mercier
Isabelle
I
Centre de Recherche de l'institut de Cardiologie de Montréal, Département de Physiologie, Université de Montréal, Montréal, Québec, Canada.
Pham-Dang
Mylan
M
Clement
Robert
R
Gosselin
Hugues
H
Colombo
Federico
F
Rouleau
Jean-Lucien
JL
Calderone
Angelino
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003619:Dansyl Compounds / Q000494:pharmacology / Q000627:therapeutic use; D004719:Endomyocardial Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D065128:Endothelin Receptor Antagonists; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010052:Ovariectomy / Q000706:statistics & numerical data; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology
D003619:Dansyl Compounds; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide