%% Papers Published
@article{fds346829,
Author = {Ahmed, S and Hu, R and Leete, J and Layton, AT},
Title = {Understanding sex differences in long-term blood pressure
regulation: insights from experimental studies and
computational modeling.},
Journal = {American Journal of Physiology Heart and Circulatory
Physiology},
Volume = {316},
Number = {5},
Pages = {H1113-H1123},
Year = {2019},
Month = {May},
url = {http://dx.doi.org/10.1152/ajpheart.00035.2019},
Abstract = {Sex differences in blood pressure and the prevalence of
hypertension are found in humans and animal models.
Moreover, there has been a recent explosion of data
concerning sex differences in nitric oxide, the
renin-angiotensin-aldosterone system, inflammation, and
kidney function. These data have the potential to reveal the
mechanisms underlying male-female differences in blood
pressure control. To elucidate the interactions among the
multitude of physiological processes involved, one may apply
computational models. In this review, we describe published
computational models that represent key players in blood
pressure regulation, and highlight sex-specific models and
their findings.},
Doi = {10.1152/ajpheart.00035.2019},
Key = {fds346829}
}
@article{fds339743,
Author = {Leete, J and Layton, AT},
Title = {Sex-specific long-term blood pressure regulation: Modeling
and analysis.},
Journal = {Computers in Biology and Medicine},
Volume = {104},
Pages = {139-148},
Year = {2019},
Month = {January},
url = {http://dx.doi.org/10.1016/j.compbiomed.2018.11.002},
Abstract = {Hypertension is a global health challenge: it affects one
billion people worldwide and is estimated to account for
>60% of all cases or types of cardiovascular disease. In
part because sex differences in blood pressure regulation
mechanisms are not sufficiently well understood, fewer
hypertensive women achieve blood pressure control compared
to men, even though compliance and treatment rates are
generally higher in women. Thus, the objective of this study
is to identify which factors contribute to the sexual
dimorphism in response to anti-hypertensive therapies
targeting the renin angiotensin system (RAS). To accomplish
that goal, we develop sex-specific blood pressure regulation
models. Sex differences in the RAS, baseline adosterone
level, and the reactivity of renal sympathetic nervous
activity (RSNA) are represented. A novel aspect of the model
is the representation of sex-specific vasodilatory effect of
the bound angiotensin II type two receptor (AT2R-bound Ang
II) on renal vascular resistance. Model simulations suggest
that sex differences in RSNA are the largest cause of female
resistance to developing hypertension due to the direct
influence of RSNA on afferent arteriole resistance.
Furthermore, the model predicts that the sex-specific
vasodilatory effects of AT2R-bound Ang II on renal vascular
resistance may explain the higher effectiveness of
angiotensin receptor blockers in treating hypertensive women
(but not men), compared to angiotensin converting enzyme
inhibitors.},
Doi = {10.1016/j.compbiomed.2018.11.002},
Key = {fds339743}
}
@article{fds346830,
Author = {Leete, J and Gurley, S and Layton, A},
Title = {Modeling Sex Differences in the Renin Angiotensin System and
the Efficacy of Antihypertensive Therapies.},
Journal = {Computers & Chemical Engineering},
Volume = {112},
Pages = {253-264},
Year = {2018},
Month = {April},
url = {http://dx.doi.org/10.1016/j.compchemeng.2018.02.009},
Abstract = {The renin angiotensin system is a major regulator of blood
pressure and a target for many anti-hypertensive therapies;
yet the efficacy of these treatments varies between the
sexes. We use published data for systemic RAS hormones to
build separate models for four groups of rats: male
normotensive, male hypertensive, female normotensive, and
female hypertensive rats. We found that plasma renin
activity, angiotensinogen production rate, angiotensin
converting enzyme activity, and neutral endopeptidase
activity differ significantly among the four groups of rats.
Model results indicate that angiotensin converting enzyme
inhibitors and angiotensin receptor blockers induce similar
percentage decreases in angiotensin I and II between groups,
but substantially different absolute decreases. We further
propose that a major difference between the male and female
RAS may be the strength of the feedback mechanism, by which
receptor bound angiotensin II impacts the production of
renin.},
Doi = {10.1016/j.compchemeng.2018.02.009},
Key = {fds346830}
}
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