(858.11) Hypogonadal Hypertension In Male Sprague-Dawley Rats Is Reversed By Testosterone and its Genomically Inactive Metabolite 5β-Dihydrotestosterone

Poster Board Number: E151

Ross Brusenhan (Texas Aamp; M University), Ahmed Oloyo (University of Lagos), John Stallone (Texas Aamp;M University)

Testosterone (TES) and its metabolites are efficacious vasodilators acutely, both in vitro and in vivo; however, their long-term effects on blood pressure (BP) are unclear. We previously reported that castration (CsX) produced hypertension (HT) in normal male rats, and long-term TES replacement therapy normalized BP and reduced renal renin-angiotensin system (RAS) expression. Thus, in the present study, the effects of TES and 5β-dihydrotestosterone (5β-DHT), a metabolite with potent and efficacious vasodilator effects but lacking classic androgenic activity, were studied in CsX male Sprague-Dawley rats. Rats were CsX at 12-13 weeks age and then studied for 15 weeks. Weekly systolic BP (by tail cuff) revealed a progressive rise in BP over 10 weeks after CsX (110 ± 1.6 vs 141 ± 1.2 mmHg). During the next 5 weeks, CsX rats received either TES (CsX + TES-enanthate, 1.75 mg/kg, 2X/week) or 5β-DHT-propionate (CsX + 5β-DHT, 2.00 mg/kg, 2X/week). BP gradually and progressively declined to normal by 5 weeks in CsX + TES rats (113 ± 1.3). In contrast, BP in CsX + 5β-DHT rats was biphasic:  a dramatic, more rapid decline to normal BP after only one week treatment (111 ± 0.7), and a continued more gradual decline to a hypotensive BP by 5 weeks (91 ± 1.1). Seminal vesicle (SV) weight after 5 weeks of androgen therapy (bioassay for androgenic activity) was 0.3250 ± 0.0180 g/100 g body weight in CsX + TES and 0.0122 ± 0.0006 in CsX + 5β-DHT. In comparison, SV weights were 0.0160 ± 0.0010 in CsX without TES and 0.2860 ± 0.0110 in intact male rats. These data suggest that:

1) endogenous and exogenous TES exert anti-HT effects in male SD rats; 2) the TES metabolite 5β-DHT exerts substantially greater, more rapid anti-HT effects which appear to involve nongenomic, androgen receptor-independent actions; and 3) while TES effects appear to involve diuretic/natriuretic effects on kidney via inhibition of renal RAS expression (our previous studies), the biphasic anti-HT effects of 5β-DHT in the present study appear to involve a rapid vasodilatory effect as well as a slower diuretic/natriuretic effect similar to that of TES.   @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-536870145 1107305727 0 0 415 0;}@font-face {font-family:Times; panose-1:0 0 5 0 0 0 0 2 0 0; mso-font-charset:0; mso-generic-font-family:auto; mso-font-pitch:variable; mso-font-signature:-536870145 1342185562 0 0 415 0;}p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0in; mso-pagination:widow-orphan; text-autospace:none; font-size:12.0pt; font-family:Times; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman";}.MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:11.0pt; mso-ansi-font-size:11.0pt; mso-bidi-font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Calibri; mso-fareast-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}.MsoPapDefault {mso-style-type:export-only; margin-bottom:10.0pt; line-height:115%;}div.WordSection1 {page:WordSection1;}

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