Although sex hormones activational effects are

Although sex hormones (activational effects) are known to directly interact with RAS (Baiardi et al., 2005, Miller et al., 1999, Silbiger and Neugarten, 1995), the potential contribution of organizational hormonal and SCC effects on physiological sex-based difference in the regulation of the RAS remains undefined. Taking into account that two of the components of the vasodilatador arm of the RAS (AT2 receptor (Agtr2) and ACE2 genes) are located in the X chromosome (Koike et al., 1994, Oudit et al., 2003) and that some genes escape X-inactivation (Carrel and Willard, 2005, Wolstenholme et al., 2013, Yang et al., 2006), it is tempting to speculate that genes residing in the SCC (which are asymmetrically inherited between males and females) may serve as candidate regulators of sexually dimorphic phenotypes. In this study, we sought to assess whether genetic differences within the SCC may differentially modulate the basal angiotensin type 1a (Agtr1a), 2 (Agtr2) and Mas (Mas1) receptor gene expression at kidney level and in Methylcobalamin nuclei involved in blood pressure regulation. We tested our hypothesis that the mRNA expression of the vasoconstrictor component (Agtr1a) of RAS would predominate in XY-SCC mice, while the vasodilator RAS components (Agtr2 and Mas1) would be enhanced in XX-SCC mice at specific brain nuclei and renal cortex levels.
Methods
Results
Discussion Although the mechanisms responsible for sexually dimorphic Ang II- bradycardic baroreflex responses are still under study, there is data indicating that the attenuation of the Ang II sexually dimorphic bradycardic baroreflex response in males may be due to central action of this peptide in the sensory circumventricular organs (CVOs). Changes in plasma and cerebrospinal fluid sodium concentration, osmolality, and Ang II/Ang 1–7 concentration are sensed by the brain, mainly in the sensory CVOs, the SFO and the OVLT in the wall of the third ventricle, and in the AP in the wall of the fourth ventricle. The fact that these nuclei are highly vascularized and contain an extensive network of fenestrated capillaries, receptor binding sites for circulating hormones like angiotensin II, atrial natriuretic peptides and vasopressin, is consistent with the proposal that these CVOs are sites at which blood-borne humoral agents exert central actions (McKinley et al., 2004). At the AP, Ang II is involved in baroreceptor reflex and blood pressure regulation. The AP is subject to both neural and humoral control and sends projections to neural centers involved in cardiovascular regulation, including the NTS, dorsal vagal complex, the parabrachial nucleus and rostral ventrolateral medulla, thereby modulating sympathetic-parasympathetic activity and baroreflex response (Blessing et al., 1987, Shapiro and Miselis, 1985). Furthermore, injury at the AP blocks the Ang II-hypertensive response and, in males, it prevents the decrease in baroreflex sensitivity observed after acute administration of this peptide (Fink et al., 1987, Xue et al., 2003). Ang II binds to AT1, inducing attenuation of the bradycardic baroreflex response, while both AT2 and Mas activation facilitate heart rate response to increases in blood pressure (Chaves et al., 2000, Gao et al., 2004, Sakima et al., 2005). Our present results on the effect of SCC on angiotensin gene expression match our previous physiological work in which we demonstrated that the bradycardic baroreflex sexual dimorphic response may be ascribed to differences in sex chromosomes (Caeiro et al., 2011). There we demonstrated that XX-SCC mice showed (irrespective of sex, XX-male and XX-female) a facilitatory bradycardic baroreflex control of heart rate and our present results consistently show an enhancement of the vasodilator component of RAS in the AP of XX-SCC mice, which may underlie the facilitation of the bradycardic baroreflex response. In contrast, the enhancement of the vasoconstrictor components of the RAS may bias XY-SCC mice towards attenuation of the bradycardic baroreflex response.