Elevations in arterial pressure are associated with increases in plasma angiotensin III and angiotensin 1‐9 in female obese SS rats prior to puberty

Abstract

Recent studies show that prepubertal obesity is associated with increased risk of hypertension in children. Moreover, previous reports have demonstrated that there is a link between the renin-angiotensin system and obesity-related hypertension via angiotensin II (Ang II) metabolism. However, to our knowledge, studies examining AngII metabolism during the development of hypertension associated with prepubertal obesity are limited. Therefore, the current study examined whether there are sex differences in arterial pressure and AngII metabolism in lean Dahl salt-sensitive (SS) and obese SS leptin receptor mutant (SSLepRmutant) rats. Four week-old female and male lean SS and obese SSLepRmutant rats (n=5 rats per group) were implanted with telemetry transmitters to measure MAP until the rats reached 8 weeks of age. Over the course of the study, we did not detect any differences MAP between female and male SS rats (115±2 and 120±2 mmHg, respectively). MAP was similar in male SSLepRmutant rats compared to their wild-type littermates (118±6 mmHg). However, we observed a marked increase in MAP in female SSLepRmutant rats compared to the other groups (144±7 mmHg; p<0.05 vs. all groups). At the end of the study, plasma was collected and analyzed for AngII metabolites (AngII, Ang(1-7), AngIII, AngIV, Ang(1-5) and Ang(1-9); via mass spectrometry). Interestingly, we did not observe any sex or strain differences in plasma AngII levels between lean SS and obese SSLepRmutant rats. Additionally, similar results were seen when measuring the plasma levels of Ang(1-7), AngIV, and Ang(1-5). However, AngIII and Ang(1-9) levels were more than two-fold higher in female obese SSLepRmutant rats versus their lean SS littermates and male obese SSLepRmutant counterparts (p<0.05 vs. all groups). Overall, these data indicate that the elevations in arterial pressure in female obese SSLepRmutant rats is associated with alterations in angiotensin metabolism with increases in plasma levels of AngIII and Ang(1-9). Additionally, further studies are needed to investigate the roles of AngIII and Ang(1-9) and their signaling pathways in the early development of hypertension in female obese SSLepRmutant rats prior to puberty.