Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2005; 11(15): 2306-2312
Published online Apr 21, 2005. doi: 10.3748/wjg.v11.i15.2306
Vascular contractile response and signal transduction in endothelium-denuded aorta from cirrhotic rats
Han-Chieh Lin, Ying-Ying Yang, Yi-Tsau Huang, Tzung-Yan Lee, Ming-Chih Hou, Fa-Yauh Lee, Shou-Dong Lee
Han-Chieh Lin, Ming-Chih Hou, Fa-Yauh Lee, Shou-Dong Lee, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan, China
Ying-Ying Yang, Institute of Clinical Medicine, National Yang-Ming University School of Medicine and Taipei Chung-Hsiao Municipal Hospital, Taipei, Taiwan, China
Yi-Tsau Huang, Tzung-Yan Lee, Institute of Traditional Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, China
Author contributions: All authors contributed equally to the work.
Supported by the National Science Council of Taiwan, No. NSC91-2314-B-075-129 and the Taipei Veterans General Hospital of Taiwan, China, No. VGH91-28
Correspondence to: Dr. Han-Chieh Lin, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 11217, Taiwan, China. hclin1956@yahoo.com
Telephone: +886-2-28757308 Fax: +886-2-28739318
Received: July 5, 2004
Revised: July 6, 2004
Accepted: August 31, 2004
Published online: April 21, 2005
Abstract

AIM: The mechanism of decreased vascular reactivity to vasoconstrictors in portal hypertension is still unclear. In addition to nitric oxide, defects in post-receptor signal transduction pathway have been suggested to play a role. However, substantial evidences observed equivocal changes of vascular reactivity following different agonists that challenged the hypothesis of the post-receptor defect. The current study was to evaluate the vascular reactivity to different agonists and the inositol trisphosphate (IP3) changes in signal transduction cascade from cirrhotic rats with portal hypertension.

METHODS: The endothelial denuded aortic rings from cirrhotic and sham-operated rats were obtained for ex vivo tension study and measurement of the corresponding [3H] IP3 formation following different receptor and nonreceptor-mediated agonists’ stimulation. Additionally, iNOS protein expression was measured in thoracic aorta. The contractile response curves to phenylephrine were performed in endothelial denuded aortic rings with and without preincubation with a specific iNOS inhibitor (L-N(6)-(1-iminoethyl)-lysine, L-NIL).

RESULTS: In endothelial denuded aortic rings of cirrhotic rats, the vascular responses were reduced with phenylephrine and arginine vasopressin (AVP) stimulation but were normal with U-46619, NaF/AlCl3, and phorbol esterdibutyrate (PdBU) stimulation. Compared to the corresponding control groups, the degree of the increment of [3H] IP3 formation from basal level was also decreased with phenylephrine and AVP stimulation, but was normal with U-46619 and NaF/AlCl3 stimulation. The preincubation with L-NIL did not modify the hyporesponsiveness to phenylephrine. Additionally, the iNOS protein expression in thoracic aorta was not different in cirrhotic and sham-operated rats.

CONCLUSION: Without the influence of nitric oxide, vascular hyporeactivity to vasoconstrictors persisted in cirrhotic rats with portal hypertension. However, the decreased vascular reactivity is an agonist-specific phenomenon. In addition, G-protein and phospholipase C pathway associated with the IP3 productions may be intact in cirrhotic rats with portal hypertension.

Keywords: Cirrhosis, Portal hypertension, Inositol trisphosphate, Vascular reactivity, Protein kinase C