title: Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring.
abstract: Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. Vascular Agtr1/Agtr2 ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect on Agtr1/Agtr2 ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.
authors.affiliation: Department of Obstetrics & Gynecology, The University of Texas Medical Branch, Galveston, Texas.
authors.forename: Kunju
authors.initials: K
authors.lastname: Sathishkumar
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors.forename: Meena P
authors.initials: MP
authors.lastname: Balakrishnan
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas cyallamp@bcm.edu.
authors.forename: Chandrasekhar
authors.initials: C
authors.lastname: Yallampalli
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D011488:Protein Deficiency / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D000726:Androgen Antagonists; D011944:Receptors, Androgen; D000804:Angiotensin II; D005485:Flutamide
keywords: Agtr1; angiotensin II; blood pressure; flutamide; mesenteric arteries; pregnancy; protein restriction; testosterone; vascular function