Acta Pharmacologica Sinica 2015-05-01

The prolactin family hormones regulate vascular tone through NO and prostacyclin production in isolated rat aortic rings.

Carmen Gonzalez, Hector Rosas-Hernandez, Brenda Jurado-Manzano, Manuel Alejandro Ramirez-Lee, Samuel Salazar-Garcia, Pedro Pablo Martinez-Cuevas, Aída Jimena Velarde-Salcedo, Humberto Morales-Loredo, Ricardo Espinosa-Tanguma, Syed F Ali, Rafael Rubio

Index: Acta Pharmacol. Sin. 36 , 572-86, (2015)

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Abstract

Prolactin family hormones include growth hormone, placental lactogen and prolactin, which are able to regulate angiogenesis via NO and prostaglandins. However, their effects on vascular tone are not fully understood. The aim of this study was to evaluate the effects of prolactin family hormones on rat vascular tone in vitro.Aortic rings were prepared from adult male rats and precontracted with phenylephrine, then treated with the hormones and drugs. The tension was measured with isometric force displacement transducer connected to a polygraph. NO production and prostacyclin release in physiological solution was determined. Cultured rat aortic endothelial cells (RAECs) were treated with the hormones and drugs, and the phosphorylation of eNOS at serine 1177 was assessed using Western bolt analysis.Administration of growth hormone or placental lactogen (0.01-100 nmol/L) induced endothelium-dependent vasodilation. Both the hormones significantly increased the phosphorylation of eNOS in RAECs and NO level in physiological solution. Preincubation with L-NAME blocked growth hormone- or placental lactogen-induced vasodilation and NO production. Preincubation with an antibody against growth hormone receptors blocked growth hormone- and placental lactogen-induced vasodilation. Addition of a single dose of prolactin (0.01 nmol/L) induced sustained vessel relaxation, whereas multiple doses of prolactin induced a biphasic contraction-relaxation effect. The vascular effects of prolactin depended on endothelium. Prolactin significantly increased the level of prostacyclin I2 in physiological solution. Preincubation with indomethacin or an antibody against prolactin receptors blocked prolactin-induced vasodilation.The prolactin family hormones regulate rat vascular tone, selectively promoting either relaxation or contraction of vascular smooth muscle via activation of either growth hormone receptors or prolactin receptors within the endothelium.