title: Enalapril Normalizes Endothelium-Derived Hyperpolarizing Factor-Mediated Relaxation in Mesenteric Artery of Adult Hypertensive Rats Prenatally Exposed to Testosterone.
abstract: Prenatal exposure to elevated testosterone levels induces adult life hypertension associated with selective impairments in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation in mesenteric arteries. We tested whether the angiotensin-converting enzyme inhibitor enalapril restores EDHF function through regulating the activities of small (Kcnn3) and intermediate (Kcnn4) conductance calcium-activated potassium channels in mesenteric arteries. Pregnant Sprague-Dawley rats were injected subcutaneously with vehicle or testosterone propionate (0.5 mg/kg/day from Gestation Day 15 to 19), and their 6-mo-old adult male offspring were examined. A subset of rats in these two groups was given enalapril (40 mg/kg/day) for 2 wk through drinking water. Blood pressures were assessed through carotid arterial catheter and endothelium-dependent mesenteric arterial EDHF relaxation, using wire myography. Ace and Kcnn3 and Kcnn4 channel expression levels were also examined. Renal and vascular Ace expression and plasma angiotensin II levels were increased in testosterone offspring. Blood pressure levels were significantly higher in testosterone offspring than in controls, and treatment with enalapril significantly attenuated blood pressure in testosterone offspring. EDHF relaxation in testosterone offspring was reduced compared to that in controls, and it was significantly restored by enalapril treatment. Kcnn4 channel expression and function were similar between control and testosterone rats, but it was not affected by enalapril treatment. Relaxation mediated by Kcnn3 was impaired in testosterone offspring, and it was normalized by enalapril treatment. Furthermore, enalapril treatment restored expression levels of Kcnn3 channels. These findings suggest that enalapril has a positive influence on endothelial function with improvement in EDHF relaxation through normalization of Kcnn3 expression and activity.
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Amar S
authors.initials: AS
authors.lastname: More
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Mishra
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.
authors.forename: Gary D V
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
authors.affiliation: Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas kusathis@utmb.edu.
authors.forename: Kunju
authors.initials: K
authors.lastname: Sathishkumar
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism*; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D013739:Testosterone; D004656:Enalapril
keywords: EDHF; Kcnn3 channel; blood pressure; enalapril; endothelium; mesenteric arteries; pregnancy; testosterone