| Autor: |
Gu Y; Department of Medicine, University of California and Veterans Affairs San Diego Healthcare System, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0838, USA., Zhang K, Biswas N, Friese RS, Lin DH, Mahata SK, Hoshijima M, O'Connor DT, Peterson KL, Brar BK |
| Jazyk: |
angličtina |
| Zdroj: |
Endocrinology [Endocrinology] 2010 Oct; Vol. 151 (10), pp. 4820-9. Date of Electronic Publication: 2010 Jul 28. |
| DOI: |
10.1210/en.2009-1454 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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