Aortic relaxation in castrated and ovariectomized rats and responses to cross sex hormone therapy (CSHT)
Poster Number
6C
Introduction/Abstract
Evidence suggests that risk factors for cardiovascular diseases (CVD) are increased in the transgender population after they undergo cross-sex hormone therapy (CSHT). Although CSHT is essential, it may increase cardiometabolic risk in both male to female (MtF) and female to male (FtM) transgender cohorts. Several reports have shown that estrogen exerts direct beneficial effects on the vessel wall in healthy females. However, the vascular effects of testosterone are conflicting. The effects of CSHT in cardiovascular physiology of males or females are even less understood.
The current study was, therefore, undertaken to evaluate the effects of estrogen and testosterone treatment on aortic reactivity in castrated (CAS) male and ovariectomized (OVX) female rats, respectively. Eight to ten weeks-old CAS male and OVX female rats were implanted subcutaneously with 1.5 mg 17β-estradiol (E2) (for CAS males) or 7.5 mg testosterone propionate (T) (for OVX females) or placebo (PL) containing pellet for about 35 days. Aged matched intact male (IM) and intact female (IF) rats were also included in the study. CAS+PL, CAS+E2 and IM were assigned in MtF group while OVX+PL, OVX+T and IF were assigned to FtM group.
Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh, 10-8 to 10-5 M) in aorta pre-contracted with phenylephrine (PE, 2 µM) was measured before and after pretreatment with indomethacin (10 µM, cyclooxygenase inhibitor), followed by L-NAME [200 µM, a nonselective nitric oxide (NO) synthase (NOS) inhibitor]. Sodium nitroprusside (SNP)-induced relaxation responses in endothelium-denuded rings in addition to the contractile responses to PE before and after L-NAME in aortic rings were also measured.
EDV to ACh was significantly impaired in CAS+E2 group compared to CAS+PL and IM rats. This impairment was accompanied by a significant decrease in NO contribution to ACh-induced relaxation. Smooth muscle sensitivity to NO, as measured by SNP relaxations, was not altered, whereas the maximum contractile responses to PE was enhanced in the aortas of CAS+E2 group compared to IM. Endothelium-derived NO release during smooth muscle contraction, as assessed by the potentiation of the response to PE after NOS inhibition, was not altered in the aortas of MtF groups. Intriguingly, neither EDV to ACh nor PE contractile responses were altered in OVX+T compared to those in OVX+PL or IF in FtM group.
Here, we provide the first evidence of impairment in aortic relaxation in CAS+E2 rats, in part via a decrease in the relative contribution of NO to the regulation of vascular relaxation responses or an increase in the contractile responses in this group. Additional studies will be needed to document the direction and underlying mechanisms of CSHT interaction with vasculatures.
Location
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Aortic relaxation in castrated and ovariectomized rats and responses to cross sex hormone therapy (CSHT)
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Evidence suggests that risk factors for cardiovascular diseases (CVD) are increased in the transgender population after they undergo cross-sex hormone therapy (CSHT). Although CSHT is essential, it may increase cardiometabolic risk in both male to female (MtF) and female to male (FtM) transgender cohorts. Several reports have shown that estrogen exerts direct beneficial effects on the vessel wall in healthy females. However, the vascular effects of testosterone are conflicting. The effects of CSHT in cardiovascular physiology of males or females are even less understood.
The current study was, therefore, undertaken to evaluate the effects of estrogen and testosterone treatment on aortic reactivity in castrated (CAS) male and ovariectomized (OVX) female rats, respectively. Eight to ten weeks-old CAS male and OVX female rats were implanted subcutaneously with 1.5 mg 17β-estradiol (E2) (for CAS males) or 7.5 mg testosterone propionate (T) (for OVX females) or placebo (PL) containing pellet for about 35 days. Aged matched intact male (IM) and intact female (IF) rats were also included in the study. CAS+PL, CAS+E2 and IM were assigned in MtF group while OVX+PL, OVX+T and IF were assigned to FtM group.
Endothelium-dependent vasorelaxation (EDV) to acetylcholine (ACh, 10-8 to 10-5 M) in aorta pre-contracted with phenylephrine (PE, 2 µM) was measured before and after pretreatment with indomethacin (10 µM, cyclooxygenase inhibitor), followed by L-NAME [200 µM, a nonselective nitric oxide (NO) synthase (NOS) inhibitor]. Sodium nitroprusside (SNP)-induced relaxation responses in endothelium-denuded rings in addition to the contractile responses to PE before and after L-NAME in aortic rings were also measured.
EDV to ACh was significantly impaired in CAS+E2 group compared to CAS+PL and IM rats. This impairment was accompanied by a significant decrease in NO contribution to ACh-induced relaxation. Smooth muscle sensitivity to NO, as measured by SNP relaxations, was not altered, whereas the maximum contractile responses to PE was enhanced in the aortas of CAS+E2 group compared to IM. Endothelium-derived NO release during smooth muscle contraction, as assessed by the potentiation of the response to PE after NOS inhibition, was not altered in the aortas of MtF groups. Intriguingly, neither EDV to ACh nor PE contractile responses were altered in OVX+T compared to those in OVX+PL or IF in FtM group.
Here, we provide the first evidence of impairment in aortic relaxation in CAS+E2 rats, in part via a decrease in the relative contribution of NO to the regulation of vascular relaxation responses or an increase in the contractile responses in this group. Additional studies will be needed to document the direction and underlying mechanisms of CSHT interaction with vasculatures.
