title: Prolactin alters blood pressure by modulating the activity of endothelial nitric oxide synthase.
abstract: Increased levels of a cleaved form of prolactin (molecular weight 16 kDa) have been associated with preeclampsia. To study the effects of prolactin on blood pressure (BP), we generated male mice with a single-copy transgene (Tg; inserted into the hypoxanthine-guanine phosphoribosyltransferase locus) that enables inducible hepatic production of prolactin and its cleavage product. The Tg is driven by the indole-3-carbinol (I3C)-inducible rat cytochrome P450 1A1 promoter. When the Tg mice were fed normal chow (NC), plasma prolactin concentrations were comparable to those in female WT mice in the last third of pregnancy, and BP was lower than in WT mice (∼95 mm Hg vs. ∼105 mm Hg). When the Tg mice were fed chow containing IC3, plasma prolactin concentrations increased threefold, BP increased to ∼130 mm Hg, and cardiac function became markedly impaired. IC3 chow did not affect the WT mice. Urinary excretion of nitrite/nitrate and the amount of Ser1177-phosphorylated endothelial nitric oxide (NO) synthase (eNOS) were significantly greater in the Tg mice fed NC than in WT mice, as they are during pregnancy. However, when I3C was fed, these indicators of NO production became significantly less in the Tg mice than in WT mice. The effects of increased plasma prolactin were abolished by a genetic absence of eNOS. Thus, a threefold increase in plasma prolactin is sufficient to increase BP significantly and to markedly impair cardiac function, with effects mediated by NO produced by eNOS. We suggest that pregnant women with abnormally high prolactin levels may need special attention.
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors: Albert S
authors: AS
authors: Chang
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors: Ruriko
authors: R
authors: Grant
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors: Hirofumi
authors: H
authors: Tomita
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors: Hyung-Suk
authors: HS
authors: Kim
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599 oliver_smithies@med.unc.edu mkakoki@med.unc.edu.
authors: Oliver
authors: O
authors: Smithies
authors: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599 oliver_smithies@med.unc.edu mkakoki@med.unc.edu.
authors: Masao
authors: M
authors: Kakoki
mesh_terms: D000818:Animals; D001794:Blood Pressure; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011388:Prolactin / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D019076:Transgenes / Q000235:genetics
chemical_list: D007211:Indoles; D009569:Nitric Oxide; D011388:Prolactin; C016517:indole-3-carbinol; D052250:Nitric Oxide Synthase Type III
keywords: hypertension; lactation; protein kinase B/Akt