TITLE:
Contribution of Estrogen to Sex Dimorphic Expression of Cardiac Natriuretic Peptide and Nitric Oxide Synthase Systems in ANP Gene-Disrupted Mice
AUTHORS:
Philip G. Wong, David W. J. Armstrong, M. Yat Tse, Nicole M. Ventura, Stephen C. Pang
KEYWORDS:
Estrogen; Atrial Natriuretic Peptide; Nitric Oxide Synthase; Sex Dimorphism; Heart
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.3 No.4B,
July
24,
2013
ABSTRACT: Background: Sex dimorphism in the prevalence, onset, development and
progression of cardiovascular disease (CVD) is well recognized, but the
mechanisms whereby sex hormones are believed to confer cardioprotection are
still not fully understood. Objective: This study more closely delineates the effect of 17β-Estradiol (E2) on the expression and signaling of the cardiac NP
and NOS systems, well-known cardioprotective modulators of the cardiac
hypertrophy (CH) response, that both contribute to downstream production of
cyclic guanosine 3’,5’-monophosphate (cGMP). Materials and Methods: Ovariectomized (OVX) female ANP+/+ and ANP-/- mice, 6 - 7 weeks old, were subjected to a five-week
treatment with E2 (100 μg/100 μL/day) or vehicle (VEH). Left ventricle from
these treatment groups, along with that from age-matched male ANP+/+ and ANP-/- mice was used to assess expression of these systems by
real-time quantitative PCR (qPCR). Left ventricle tissue and plasma cGMP were
measured by enzyme immunoassay to assess alterations in resultant downstream
signaling. Results: NP system
expression was unchanged across genotype, sex and E2 treatment. Sex-specific
differences in NOS system expression were observed; female mice showed an
increased expression of NOS system genes that were significantly elevated in
all but one of the E2 treatment groups. Left ventricle tissue cGMP remained
unchanged across genotype, sex and E2 treatment. Plasma cGMP levels were
unchanged in ANP+/+ treatment groups. In ANP-/- treatment
groups, plasma cGMP in the female OVX-E2 mice was significantly higher compared
to male and female OVX-VEH mice. Conclusion: These findings demonstrate that in the absence of ANP, E2 upregulates cardiac
NOS system expression to produce cGMP. This study confirms the importance of
the cardiac NOS system in females; this particular system may be a promising
future target for sex-specific treatments and therapies for CVD in women.