The chronic blockade of angiotensin I-converting enzyme eliminates the sex differences of serum cytokine levels of spontaneously hypertensive rats

Sex hormones modulate the action of both cytokines and the renin-angiotensinsystem. However, the effects of angiotensin I-converting enzyme (ACE) on theproinflammatory and anti-inflammatory cytokine levels in male and femalespontaneously hypertensive rats (SHR) are unclear. We determined therelationship between ACE activity, cytokine levels and sex differences in SHR.Female (F) and male (M) SHR were divided into 4 experimental groups each (n =7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage),castrated + vehicle, and castrated + enalapril. Treatment began 21 days aftercastration and continued for 30 days. Serum cytokine levels (ELISA) and ACEactivity (fluorimetry) were measured. Male rats exhibited a higher serum ACEactivity than female rats. Castration reduced serum ACE in males but did notaffect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV =16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV =12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levelswere higher in females than in males. Ovariectomy reduced all cytokine levelsand orchiectomy reduced IL-6 but increased IL-10 concentrations in males.Castration eliminated the differences in all inflammatory cytokine levels (IL-6and TNF-α) between males and females. Enalapril increased IL-10 in all groupsand reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalaprileliminated the sexual dimorphisms of cytokine levels in SV animals, whichsuggests that enalapril exerts systemic anti-inflammatory and anti-hypertensiveeffects.