Oral presentation: Sex Chromosome Complement is responsible for Ang II-mediated bradycardic gender differences.

CAEIRO XIMENA; MIR FRANCO; VIVAS LAURA; CAMBIASSO M JULIA

Washington, D.C., USA

Congreso; Council for High Blood Pressure Research- High Blood Pressure Research 2010 Scientific Sessions.; 2010

Sex chromosome complement is responsible for Ang II-mediated bradycardic gender differences Ximena Caeiro, Franco Mir, Laura Vivas, Maria Julia Cambiasso. The purpose of this study was to test the hypothesis that sex chromosomal complement (SCC) is responsible for gender differences in Ang II-bradycardic baroreflex response. 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, chronically implanted with arterial and venous catheters, 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). 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.   These data support the hypothesis that Ang II-mediated acute blunting of baroreflex regulation of HR may be under  the control of SCC regardless of the gonadal status.