Function of Urotensin

The contractile effects of urotensin vary in different species and vascular beds (7982). Lim et al. (83) observed that urotensin mediated a dose-dependent vasodilation in healthy subjects but that a dose-dependent vasoconstriction occurred in patients with

Fig. 7. Correlation of human urotensin Il-like immunoreactivity (hU-II-LI) with (A) LVEF and (B) LVEDP. Shown are the raw data. Pearson's correlation coefficient was calculated with log-transformed hU-II-LI values (A,B). (C) hU-II-LI in different NYHA classes. Raw data with the mean ± SEM next to the column scatters are presented. (D) Box plots with log-transformed hU-II-LI for different NYHA classes. The results of group comparison are shown. NYHA IV is not included because there was only one patient. (Reproduced from ref. 75.)

Fig. 7. Correlation of human urotensin Il-like immunoreactivity (hU-II-LI) with (A) LVEF and (B) LVEDP. Shown are the raw data. Pearson's correlation coefficient was calculated with log-transformed hU-II-LI values (A,B). (C) hU-II-LI in different NYHA classes. Raw data with the mean ± SEM next to the column scatters are presented. (D) Box plots with log-transformed hU-II-LI for different NYHA classes. The results of group comparison are shown. NYHA IV is not included because there was only one patient. (Reproduced from ref. 75.)

heart failure when urotensin was iontophoresed to the skin microvasculature, suggesting that urotensin may contribute to increased peripheral vascular resistance in heart failure.

In addition to the contractile effects of urotensin, Onan et al. (84) recently demonstrated a strong hypertrophic growth effect of urotensin in neonatal cardiac myocytes when expression of the urotensin receptor was experimentally increased. Urotensin activates the ERK1/2 and p38 MAPK pathways through mechanisms involving the epidermal growth factor receptor (84). Urotensin induces proliferation of cultured VSMCs via phosphorylation ofERK1/2 (85). These studies (84,85) in cardiovascular cell types (cardiac myocytes, SMCs, and fibroblasts) confirm a previous finding that, in addition to its calcium mobilization effect characteristic of G protein receptor signaling, urotensin signaling caused activation of the ERK1/2 MAPK pathway in an experimental cell culture system (86).

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