Urocortin 2 Lowers Blood Pressure and Reduces Plasma Catecholamine Levels in Mice with Hyperadrenergic Activity
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ID: 271297
2010
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Abstract
Exaggerated adrenergic activity is associated with human hypertension. The peptide urocortin 2 (Ucn 2) inhibits catecholamine synthesis and secretion from adrenal chromaffin cells in vitro and administration to mammals lowers blood pressure (BP). The chromogranin A-null mouse (Chga−/−) manifests systemic hypertension because of excessive catecholamine secretion from the adrenal and decreased catecholamine storage. In the present study, we investigated whether systemic administration of Ucn 2 could reduce BP and adrenal and plasma levels of catecholamines in vivo. Ucn 2 peptide was administered to freely moving, conscious Chga−/− and wild-type control mice. Telemetry and HPLC measured changes in BP and catecholamine levels, respectively. In both groups of mice, Ucn 2 dose-dependently decreased BP, and this effect was mediated by corticotropin factor-receptor type 2. However, in Chga−/− mice, the maximal percentage decrease of systolic BP from basal systolic BP was 37% compared with only a 23% reduction in wild-type mice (P = 0.04). In Chga−/− mice only, Ucn 2 decreased adrenal and plasma levels of catecholamines as well as adrenal levels of tyrosine hydroxylase protein and phosphorylation. In vitro mechanistic studies demonstrated that Ucn 2 reduces both catecholamine secretion and tyrosine hydroxylase promoter activity, suggesting that the exaggerated action of Ucn 2 to reduce BP in the Chga−/− mouse is mediated through inhibition of both catecholamine synthesis and secretion. The data suggest that Ucn 2 may be therapeutically useful in regulating the exaggerated sympathoadrenal function of hyperadrenergic hypertension.
| Reference Key |
brar2010endocrinologyurocortin
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| Authors | Yusu Gu,Kuixing Zhang,Nilima Biswas,Ryan S. Friese,Dennis H. Lin,Sushil K. Mahata,Masahiko Hoshijima,Daniel T. O'connor,Kirk L. Peterson,Bhawanjit K. Brar;Yusu Gu;Kuixing Zhang;Nilima Biswas;Ryan S. Friese;Dennis H. Lin;Sushil K. Mahata;Masahiko Hoshijima;Daniel T. O'connor;Kirk L. Peterson;Bhawanjit K. Brar; |
| Journal | endocrinology |
| Year | 2010 |
| DOI |
10.1210/en.2009-1454
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| URL | |
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