scholarly journals Gonadal hormone‐independent sex differences in GABA A receptor activation in rat embryonic hypothalamic neurons

2020 ◽  
Vol 177 (13) ◽  
pp. 3075-3090 ◽  
Author(s):  
Franco R. Mir ◽  
Carlos Wilson ◽  
Lucas E. Cabrera Zapata ◽  
Luis G. Aguayo ◽  
María Julia Cambiasso
Keyword(s):  
Sex Differences ◽  
Receptor Activation ◽  
Gonadal Hormone ◽  
Hypothalamic Neurons ◽  
Gaba A

Mineralocorticoid receptors and the heart, multiple cell types and multiple mechanisms: a focus on the cardiomyocyte

2013 ◽  
Vol 125 (9) ◽  
pp. 409-421 ◽  
Author(s):  
Laura A. Bienvenu ◽  
Melissa E. Reichelt ◽  
Lea M. D. Delbridge ◽  
Morag J. Young
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Sex Differences ◽  
Side Effects ◽  
Therapeutic Option ◽  
Cell Types ◽  
Receptor Activation ◽  
Cardiac Events ◽  
Cardiac Tissues ◽  
Targeted Interventions

MR (mineralocorticoid receptor) activation in the heart plays a central role in the development of cardiovascular disease, including heart failure. The MR is present in many cell types within the myocardium, including cardiomyocytes, macrophages and the coronary vasculature. The specific role of the MR in each of these cell types in the initiation and progression of cardiac pathophysiology is not fully understood. Cardiomyocyte MRs are increasingly recognized to play a role in regulating cardiac function, electrical conduction and fibrosis, through direct signal mediation and through paracrine MR-dependent activity. Although MR blockade in the heart is an attractive therapeutic option for the treatment of heart failure and other forms of heart disease, current antagonists are limited by side effects owing to MR inactivation in other tissues (including renal targets). This has led to increased efforts to develop therapeutics that are more selective for cardiac MRs and which may have reduced the occurrence of side effects in non-cardiac tissues. A major clinical consideration in the treatment of cardiovascular disease is of the differences between males and females in the incidence and outcomes of cardiac events. There is clinical evidence that female sensitivity to endogenous MRs is more pronounced, and experimentally that MR-targeted interventions may be more efficacious in females. Given that sex differences have been described in MR signalling in a range of experimental settings and that the MR and oestrogen receptor pathways share some common signalling intermediates, it is becoming increasingly apparent that the mechanisms of MRs need to be evaluated in a sex-selective manner. Further research targeted to identify sex differences in cardiomyocyte MR activation and signalling processes has the potential to provide the basis for the development of cardiac-specific MR therapies that may also be sex-specific.

scholarly journals Endothelin, sex, and pregnancy: unique considerations for blood pressure control in females

2016 ◽  
Vol 310 (8) ◽  
pp. R691-R696 ◽  
Author(s):  
Ellen E. Gillis ◽  
Jennifer M. Sasser ◽  
Jennifer C. Sullivan
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Blood Pressure Control ◽  
Pressure Control ◽  
Receptor Activation ◽  
Receptor Expression ◽  
Young Females ◽  
Potential Benefits ◽  
Important Pathway ◽  
Potent Vasoconstrictor

Endothelin-1 (ET-1) is a potent vasoconstrictor, and dysregulation of the endothelin (ET) system has been implicated in the development of hypertension. Sex differences in the ET system have been identified in ET receptor expression and activation, levels of ET-1, and downstream mediators of the ET system. More specifically, males have greater ET-1/ETA receptor activation, whereas females exhibit greater ETB receptor activation. These differences have been suggested to contribute to the sex differences observed in blood pressure control, with greater ETB receptor activation in females potentially acting as an important pathway contributing to the lower prevalence of hypertension in young females compared with age-matched males. This hypothesis is further supported by studies in pregnancy; the role of the ET system is enhanced during pregnancy, with dysregulation of the ET system resulting in preeclampsia. Further research is necessary to elucidate the relative roles of the ET system in blood pressure control in both sexes and to further explore the potential benefits of pharmacological ET blockade in women.

scholarly journals Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases

2010 ◽  
Vol 298 (4) ◽  
pp. H1146-H1154 ◽  
Author(s):  
Jianjie Wang ◽  
Susan Bingaman ◽  
Virginia H. Huxley
Keyword(s):  
Sex Differences ◽  
Barrier Function ◽  
Vascular Function ◽  
Gonadal Hormones ◽  
Female Rats ◽  
Gonadal Hormone ◽  
Microvascular Endothelial Cell ◽  
Mrna Levels ◽  
Male And Female Rats ◽  
Microvascular Endothelial

The importance of gonadal hormones in the regulation of vascular function has been documented. An alternate and essential contribution of the sex chromosomes to sex differences in vascular function is poorly understood. We reported previously sex differences in microvessel permeability ( Ps) responses to adenosine that were mediated by the cAMP signaling pathway (Wang J, PhD thesis, 2005; Wang J and Huxley V, Proceedings of the VIII World Congress of Microcirculation, 2007 ; Wang J and Huxley VH, Am J Physiol Heart Circ Physiol 291: H3094–H3105, 2006). The two cyclic nucleotides, cAMP and cGMP, central to the regulation of vascular barrier integrity, are hydrolyzed by phosphodiesterases (PDE). We hypothesized that microvascular endothelial cells (EC) would retain intrinsic and inheritable sexually dimorphic genes with respect to the PDEs modulating EC barrier function. Primary cultured microvascular EC from skeletal muscles isolated from male and female rats, respectively, were used. SRY (a sex-determining region Y gene) mRNA expression was observed exclusively in male, not female, cells. The predominant isoform among PDE1–5, present in both XY and XX EC, was PDE4. Expression mRNA levels of PDE1A (male > female) and PDE3B (male < female) were sex dependent; PDE2A, PDE4D, and PDE5A were sex independent. Barrier function, Ps, was determined from measures of albumin flux across confluent primary cultured microvessel XY and XX EC monolayers. Consistent with intact in situ microvessels, basal monolayer Ps did not differ between XY (1.7 ± 0.2 × 10−6 cm/s; n = 8) and XX (1.8 ± 0.1 × 10−6 cm/s; n = 10) EC. Cilostazol, a PDE3 inhibitor, reduced (11%, P < 0.05) Ps in XX, not XY, cells. These findings demonstrate the presence and maintenance of intrinsic sex-related differences in gene expression and cellular phenotype by microvascular EC in a gonadal-hormone-free environment. Furthermore, intrinsic cell-sex likely contributes significantly to sexual dimorphism in cardiovascular function.

Sex differences in the control of neuronal nitric oxide synthase by GABA-A receptors in the developing rat diencephalon

2007 ◽  
Vol 1149 ◽  
pp. 38-49 ◽  
Author(s):  
Athanasios Mantelas ◽  
Antonios Stamatakis ◽  
Maria Fameli ◽  
Fotini Stylianopoulou
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Gaba A ◽  
Oxide Synthase ◽  
Developing Rat
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