Sex-specific impact of angiotensin II on arterial pressure and LV mass during angiotensin converting enzyme inhibition in spontaneously hypertensive rats

Sex differences in arterial pressure responses to angiotensin II (AngII) have been noted, particularly in normotensive animals. In addition, sex-specific changes in renin angiotensin system (RAS) components have been implicated in differential regulation of arterial pressure between males and females. The present study evaluated the sex-specific responses to AngII infusion, angiotensin converting enzyme inhibitor (ACEi) treatment, and AngII infusion during ACEi treatment on mean arterial pressure (MAP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). Young adult male and female SHR were treated with the ACEi, enalapril (30mg/kg per day, p.o.) alone or in combination with AngII at a low (200 ng/kg per min) or high (400 ng/kg per min) dose for two weeks. MAP was measured by radiotelemetry and data presented as percent change from pre-treatment baseline. At time of sacrifice, left ventricles were excised and weighed and normalized to body weight. ACEi induced equivalent percent reductions in MAP between male (-21 ± 1.2%) and female (-23 ± 1.9%) SHR. AngII (high) infusion significantly increased MAP, with a tendency toward a greater effect in male compared to female SHR (male: 29 ± 4.6% vs. female: 17 ± 3.6%, p=0.09). During ACEi, low dose Ang II did not significantly impact the antihypertensive effect of ACEi in males or females. However, administration of the high dose of AngII during ACEi resulted in a marked sex difference whereby the male SHR exhibited an increase in arterial pressure (ACEi: -21.22% ± 1.21, ACEi+AngII high: +39.49% ± 1.39, p<0.05), while in females AngII had no impact on the depressor response to ACEi alone (ACEi: -22.59% ± 1.89, ACEi+AngII high: -18.14% ± 0.88, p>0.05). Evaluation of left ventricular hypertrophy (LVH) revealed a similar sex difference. The low dose of AngII prevented the reversal of LVH induced by ACEi in male (Con: 2.54 ± 0.09, ACEi: 1.99 ± 0.04*, ACEi+AngII: 2.34 ± 0.13†, *p<0.05 vs. Con, †p<0.05 vs. ACEi), but not female rats (Con: 2.95 ± 0.02, ACEi: 2.43 ± 0.04*, ACEi+AngII: 2.46 ± 0.09*, *p<0.05 vs. Con). In summary, ACEi produces equivalent reductions in arterial pressure and LVH in male and female SHR when the endogenous RAS is intact. However, inhibition of the RAS reveals a marked sex difference in the responsiveness to AngII both with respect to arterial pressure and cardiac hypertrophic responses. Gaining a greater understanding of sex differences in blood pressure control will ultimately lead to improved antihypertensive cardioprotective therapies for women. R01HL153112-02 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.