Endocrinology, Vol 134, 2230-2236, Copyright © 1994 by Endocrine Society

ARTICLES

Mechanical stimuli induce vascular parathyroid hormone-related protein gene expression in vivo and in vitro

CJ Pirola, HM Wang, MI Strgacich, A Kamyar, B Cercek, JS Forrester, TL Clemens and JA Fagin
Division of Cardiology, Cedars-Sinai Medical Center, University of California School of Medicine, Los Angeles 90048.

PTH-related peptide (PTHrP), the factor mediating the syndrome of humoral hypercalcemia of malignancy, is also expressed in smooth muscle cells (SMC) of the urinary bladder and uterus in response to mechanical distention and fetal occupancy, respectively. Vascular SMC also produce PTHrP, and its expression is induced by serum and vasoconstrictors, such as angiotensin-II. To determine whether mechanical distension affected vascular PTHrP gene expression, the abdominal aorta of adult male rats was balloon-distended, and aortae were collected at various times after the intervention. PTHrP mRNA was determined by competitive reverse transcriptase-polymerase chain reaction, using sequential dilutions of a cloned internally truncated PTHrP RNA fragment as standard. The molar concentration of PTHrP mRNA was obtained by extrapolating at a standard/wild-type band intensity ratio of 1:1. Aortic PTHrP mRNA was induced from a basal level of 19, to 22, 46, 36, 13, 12, 22, and 20 attamoles/mg total RNA 1, 2, 12, 24, and 48 h and 7 and 48 days after balloon distension, respectively. To determine whether mechanical events directly regulate vascular PTHrP gene expression, primary rat aortic SMC were plated and placed on a rocking device at 20 oscillations/min to create a gentle flowing motion of the culture medium. Rocking induced PTHrP mRNA of SMC exposed to either serum-free medium or 10% serum by 2.5-and 4.0-fold at 4 h, and 2.9- and 3.7-fold at 24 h, respectively. These effects were oscillation rate dependent, potentiated by angiotensin-II, and specific, as similar changes were not observed in alpha-actin mRNA content. Flow motion- induced PTHrP mRNA at 24 h was partially decreased by 10(-6) M colchicine (which inhibits microtubule assembly), but not by cytochalasin-E (which disrupts actin polymerization). As PTHrP is a known vasorelaxant, we propose that mechanical events induce the release of PTHrP by SMC, possibly to serve as a compliance factor or an agent for vascular remodeling.

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