title: Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring.
abstract: Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg.kg(-1).day(-1)) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 +/- 3 mmHg) and control (110 +/- 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng.kg(-1).min(-1) for 30 min) was observed in growth-restricted (160 +/- 2 mmHg) vs. control (136 +/- 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 +/- 2 mmHg) rats with no significant effect on blood pressure in controls (130 +/- 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 microg/min) in control (184 +/- 5 mmHg) and growth-restricted (184 +/- 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505, USA.
authors.forename: Norma B
authors.initials: NB
authors.lastname: Ojeda
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Royals
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Black
authors.forename: John Henry
authors.initials: JH
authors.lastname: Dasinger
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Johnson
authors.forename: Barbara T
authors.initials: BT
authors.lastname: Alexander
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001724:Birth Weight / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004326:Drinking / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology*; D007668:Kidney / Q000033:anatomy & histology / Q000502:physiology; D008297:Male; D009919:Orchiectomy; D009929:Organ Size / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012737:Sex Factors; D013739:Testosterone / Q000097:blood / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D013739:Testosterone