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Cardiovascular Research 1998 39(3):651-656; doi:10.1016/S0008-6363(98)00176-X
© 1998 by European Society of Cardiology
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Copyright © 1998, European Society of Cardiology

Impaired paracrine effect of endothelin-1 on vascular smooth muscle in streptozotocin-diabetic rats

Sheng-Qian Wu1 and Fai Tang*

Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong, China

* Corresponding author. Tel.: +852-2819-9269; Fax: +852-2855-9730; E-mail: ftang@hkucc.hku.hk

Objective: This study was to examine the effect of streptozotocin-induced diabetes on endothelin-1 and its receptors in the mesenteric artery and in the thoracic aorta. Methods: Diabetes was induced in SD rats by streptozotocin. Insulin was given subcutaneously. Endothelin-1 levels in the plasma, thoracic aorta and mesenteric artery were measured using radioimmunoassay. The Bmax and Kd values of endothelin-1 receptors in the mesenteric artery and in the thoracic aorta were analyzed using Scatchard plot analysis. Preproendothelin mRNA levels were examined using RT-PCR. Results: Endothelin-1 levels in the mesenteric artery (83.6±6.9 pg/mg protein) and in the thoracic aorta (73.9±8.2 pg/mg protein) increased in 2 week diabetic rats compared with both control (51.8±5.3, 46.3±5.9 pg/mg protein) and insulin treated rats (65.6±8.1, 48.1±4.2 pg/mg protein) but not in 4 week diabetic rats. There was no change in plasma endothelin-1 levels in these diabetic rats. The RT-PCR results indicated that preproendothelin mRNA levels in the mesenteric artery (0.38±0.02 vs 0.52±0.05 units) and in the thoracic aorta (0.45±0.06 vs 0.62±0.03 units) decreased in 4 week diabetic rats but not in 2 week diabetic rats. A significant increase in Kd and Bmax of endothelin receptors in the mesenteric artery and in the thoracic aorta was observed in both 2 week (about 70%) and 4 week (80–85%) diabetic rats. Insulin replacement reversed the effects of diabetes on endothelin-1 peptide contents, preproendothelin mRNA levels and the binding activity in the blood vessels. Conclusion: Increased endothelin peptide content with no change in mRNA or decreased mRNA levels with no change in peptide content together with increased receptor binding sites and affinities might imply a decrease in endothelin release and therefore an impaired paracrine effect of endothelin on vascular smooth muscles in these STZ-diabetic rats.

KEYWORDS Endothelin; Diabetes; Paracrine; Rat; Receptors; Vascular smooth muscle

1 Present address: Department of Physiology, Beijing Medical University, Beijing 100083, China.


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