Effect of sex chromosome complement (SCC) and gonadal steroids on sexual dimorphic Ang II-mediated functions.

VIVAS, L; CAEIRO X.; CAMBIASSO, MJ

Ribeirao Preto, San Pablo

Simposio; “Recent advances in the study of the Integrative Physiology with emphasis on the neuroendocrine control of energy metabolism and body fluid homeostasis”.; 2012

Facultad de Medicina Ribeirao Preto, Universidad de San pablo.

Effect of sex chromosome complement (SCC) and gonadal steroids on sexual dimorphic Ang II-mediated functions. Laura Vivas, Ximena Caeiro and Julia Cambiasso. Ferreyra Institute, Cordoba-Argentina. Gender differences in Ang II-bradycardic baroreflex response and sodium appetite induced by fluid depletion (mainly dependent of the rennin angiotensin system activity) has been previously shown. In this symposium we will discuss our studies in order to test the hypothesis that SCC is in part responsible for gender differences in these homeostatic functions mediated by angiotensin. To this end, we used the four core genotype mouse model in which gonadal sex is separated from the SCC enabling comparisons among XX and XY females and XX and XY males. This mouse model incorporates a spontaneous mutation of the Sry gene on the Y sex chromosome (referred to as Y−) and a Sry transgene that randomly inserts on an autosome, thus, testes determination is disassociated from SCC. As a result, all individuals possessing the Sry transgene develop testes, regardless of their SCC, while individuals lacking the transgene have ovaries. The resulting genotypes are XX and XY− females (ovary-bearing) along with XXSry and XY−Sry males (testes-bearing). The present study evaluated in conscious gonadectomized male and female mice: 1- The involvement of SCC on baroreflex regulation of heart rate (HR) in response to changes in blood pressure  evoked by phenylephrine (PE, 1.0 mg/ml), ANG II (100 mg/ml) and sodium nitroprusside (SNP, 6.0 ìg/min), in chronically implanted mice with arterial and venous catheters. The administration of PE in XY- mice resulted in a significantly lower baroreflex  response  than that reported for the other genotypes (slope of regression line for  XY-: -3,41 ± 0,79 beats.min-1.mmHg-1 vs -6,5 ± 0,5; -7,9±0,5 and -7,1±0,6 beats.min-1.mmHg-1 in XY-Sry, XXSry and XX mice respectively). However, in XY-Sry male and XY- female mice, the ANG II- bradycardic baroreflex response was significantly less than that induced in XX female nor in XXSry male mice (-3,8±0,7 and -3,1±0,5 beats.min-1.mmHg-1 in XY-Sry and XY- mice vs. -6,7±0,4 and -6,4±0,7 beats.min-1.mmHg-1 in XX and XXSry mice). These results indicate that animals with XY SCC show a lesser significant decrease in HR induced by Ang II when compared to the response observed in mice with the XX SCC. Additionally, no differences in the SNP-HR response were observed in mice from different genotypes.  The results here reported indicate that the bradicardic Ang II-sexually dimorphic response is directly triggered by genetic mechanisms with none hormonal intermediate. The results of this study could therefore help to further explain the origins for the sexually dimorphic action of Ang II in the regulation of baroreceptor reflex response and add more detail the foundation sources of the differences in cardiovascular responses observed between male and females. 2-We also evaluated whether genetic differences associated with SCC may differentially modulate specific sodium appetite and the pattern of neuronal activation due to physiological stimulation of the rennin-angiotensin system. In this case adult mice of the four core genotype mouse model aged 45-50 days old were also gonadectomized and after a 15-day-recovery period, they were placed in individual metabolic and subjected to acute sodium depletion. Twenty-one hours after the administration of Furosemide or vehicle solution the animals were perfused and the brains stored until further immunohistochemical processing of Fos, used as a marker of neuronal activation. In summary, these results indicated that sodium appetite is under the influence of the organizational effect of the gonadal steroids regardless of SCC of the animals, besides they showed a modulatory effect of SCC on brain activity of central areas closely related to hidroelectrolyte homeostasis like the subfornical organ and the area postrema. Supported by ANPCyT, CONICET and SECyT.