Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring.
Our laboratory uses a model of intrauterine growth restriction (IUGR) induced by placental insufficiency in the rat to examine the developmental origins of adult disease. In this model only male IUGR offspring remain hypertensive in adulthood, revealing sex-specific differences. The purpose of this study was to determine whether testosterone with participation of the renin-angiotensin system (RAS) contributes to hypertension in adult male IUGR offspring. At 16 wk of age a significant increase in testosterone (346 +/- 34 vs. 189 +/- 12 ng/dl, P < 0.05) was associated with a significant increase in mean arterial pressure (MAP) measured by telemetry in IUGR offspring (147 +/- 1 vs. 125 +/- 1 mmHg, P < 0.05, IUGR vs. control, respectively). Gonadectomy (CTX) at 10 wk of age significantly reduced MAP by 16 wk of age in IUGR offspring (124 +/- 2 mmHg, P < 0.05 vs. intact IUGR) but had no effect in control (125 +/- 2 mmHg). A significant decrease in MAP in intact IUGR (111 +/- 3 mmHg, P < 0.05 vs. untreated intact IUGR) and castrated IUGR (110 +/- 4 mmHg, P < 0.05 vs. untreated CTX IUGR) after treatment with enalapril for 2 wk suggests a role for RAS involvement. However, the decrease in blood pressure in response to enalapril was greater in intact IUGR (Delta36 +/- 1 mmHg, P < 0.05) compared with CTX IUGR (Delta15 +/- 2 mmHg), indicating an enhanced response to RAS blockade in the presence of testosterone. Thus these results suggest that testosterone plays a role in modulating hypertension in adult male IUGR offspring with participation of the RAS.
Ojeda
Norma B
NB
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA.
Grigore
Daniela
D
Yanes
Licy L
LL
Iliescu
Radu
R
Robertson
Elliot B
EB
Zhang
Huimin
H
Alexander
Barbara T
BT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001724:Birth Weight / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000502:physiology; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D009919:Orchiectomy; D010920:Placenta / Q000098:blood supply; D010927:Placental Insufficiency / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012727:Sex Characteristics; D013686:Telemetry; D013739:Testosterone / Q000097:blood / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013739:Testosterone; D004656:Enalapril; D012083:Renin