Title

Aortic Relaxation in Castrated Male Rats and Responses to Estrogen Treatment

Poster Number

2B

Lead Author Affiliation

Molecular and Cellular Pharmacology

Lead Author Status

Doctoral Student

Second Author Affiliation

Postdoctoral Fellow

Third Author Affiliation

Biopharmaceutical Science

Third Author Status

Doctoral Student

Fourth Author Affiliation

Department of Pharmaceutical Sciences and Medicinal Chemistry

Fourth Author Status

Faculty

Fifth Author Affiliation

Physiology and Pharmacology

Fifth Author Status

Faculty

Introduction

Previous studies suggest that risk factors for cardiovascular diseases (CVD) have increased in the transgender population after they undergo cross-sex hormone therapy (CSHT). Several studies, including ours in animal models as well as in humans, have shown that estrogen exerts direct beneficial effects on the vessel wall in healthy females. A growing body of evidence also suggests that androgen exhibits protective actions on the cardiovascular system. However, the effects of CSHT in cardiovascular physiology in males or females are less understood.

Purpose

The current study was, therefore, undertaken to evaluate the effects of estrogen treatment on aortic reactivity in castrated (CAS) male rats. Specifically, we investigated the effects of 17β-estradiol (E2) treatment on the aortic responses of CAS+E2 rats compared to that in the intact male (IM), placebo-treated (CAS+PL) and E2-treated ovariectomized (OVX+E2) rats.

Method

Age-matched Sprague Dawley male and female rats were gonadectomized and implanted subcutaneously with either E2 (1.5 mg) or a placebo-containing pellet for 30 days. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine (ACh, 10-8 to 10-5 M) in aorta precontracted with phenylephrine (PE, 2 µM) was measured before and after pretreatment with indomethacin (10 µM, cyclooxygenase inhibitor), followed by N-nitro- L-arginine methyl ester [L-NAME, 200 µM, a nonselective nitric oxide synthase (NOS) inhibitor]. The contractile response curves to PE (10-8 to 10-5 M) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP, 10-9 to 10-5 M) in endothelium-denuded rings were also measured.

Results

EDV to ACh was significantly impaired in aortic rings from CAS+E2 rats compared to the IM, CAS+PL and OVX+E2 rats. The impairment of EDV to ACh in CAS+E2 rats was accompanied by a significant decrease in nitric oxide (NO) contribution to ACh-induced vasorelaxation in this group. The smooth muscle sensitivity to NO as measured by SNP relaxation response curve was not altered, whereas the responsiveness to PE was enhanced in the aortas of CAS+E2 group compared to the IM group.

Significance

Overall, our data demonstrate that aortic function was impaired in CAS+E2 rats. Here, we provide the first evidence of impairment in aortic relaxation in CAS+E2 rats, possibly via a significant decrease in the relative contribution of NO to the regulation of vascular relaxation response. Furthermore, the comparison of current data in the CAS+PL with the IM appears to rule out any effect of testosterone deprivation on the stimulated release of NO in male rat aortas. Additional studies will be conducted to document the effect of CSHT interaction on vasculatures (Supported by NIDA/NIGMS, 1SC1DA052120-01 to MF and the University of the Pacific).

Location

William Knox Holt Memorial Library and Learning Center, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211

Format

Poster Presentation

Poster Session

Morning

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Apr 30th, 10:00 AM Apr 30th, 12:00 PM

Aortic Relaxation in Castrated Male Rats and Responses to Estrogen Treatment

William Knox Holt Memorial Library and Learning Center, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211

Previous studies suggest that risk factors for cardiovascular diseases (CVD) have increased in the transgender population after they undergo cross-sex hormone therapy (CSHT). Several studies, including ours in animal models as well as in humans, have shown that estrogen exerts direct beneficial effects on the vessel wall in healthy females. A growing body of evidence also suggests that androgen exhibits protective actions on the cardiovascular system. However, the effects of CSHT in cardiovascular physiology in males or females are less understood.