Effects of arginine vasopressin on growth of rat cardiac fibroblasts: role of V1 receptor.
The abnormal proliferation of cardiac fibroblasts is involved in the pathophysiologic process of left ventricular hypertrophy (LHV) associated with essential hypertension. Arginine vasopressin (AVP) has been reported to contribute significantly to the pathogenesis of hypertension. In this study, the authors investigated the effects of AVP and its V1 receptor antagonist [d(CH2)5Tyr2(Me)]AVP on the growth of rat cardiac fibroblasts. Cardiac fibroblasts of neonatal Sprague-Dawley rats were isolated, and growth-arrested cardiac fibroblasts were stimulated with 2.5% fetal calf serum in the presence and absence of AVP (0.001, 0.01, 0.1, and 1 microM) and [d(CH2)5Tyr2(Me)]AVP (0.1 microM). DNA synthesis was measured by [3H]thymidine incorporation. Thiazolyl blue assay and flow cytometry techniques were adopted to measure cell numbers and analyze cell cycle, respectively. Arginine vasopressin (0.1 and 1 microM) significantly increased DNA synthesis in cardiac fibroblasts. Moreover, AVP (0.1 and 1 microM) significantly increased the number of cardiac fibroblasts. Analysis of cell cycle showed that AVP (0.1 microM) increased S-stage percentage and proliferation index (PI). The V1 receptor antagonist [d(CH2)5Tyr2(Me)]AVP (0.1 microM) significantly inhibited DNA synthesis in cardiac fibroblasts. The cell number, S-stage percentage, and PI induced by AVP (0.1 microM) were significantly decreased by [d(CH2)5Tyr2(Me)]AVP (0.1 microM). These findings suggest that AVP might promote the proliferation of rat cardiac fibroblasts, which seems to be mediated via the V1 receptor. Arginine vasopressin may be involved in the pathophysiologic process of LVH by promoting cardiac fibroblast proliferation.
Yang
Xue-Dong
XD
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, ShaanXi Province, China.
Zhao
Lian-You
LY
Zheng
Qiang-Sun
QS
Li
Xue
X
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D017379:Hypertrophy, Left Ventricular / Q000209:etiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism*
D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D004247:DNA