Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, NG-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B2 receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.
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November 07 2000
Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin
Chi-Jen CHU;
Chi-Jen CHU
*National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Shwu-Ling WU;
Shwu-Ling WU
†National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Fa-Yauh LEE;
*National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
Correspondence: Dr Fa-Yauh Lee (e-mail [email protected]).
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Sun-Sang WANG;
Sun-Sang WANG
†National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Full-Young CHANG;
Full-Young CHANG
*National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Han-Chieh LIN;
Han-Chieh LIN
*National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Che-Chang CHAN;
Che-Chang CHAN
†National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Shou-Dong LEE
Shou-Dong LEE
*National Yang-Ming University School of Medicine, No-155, Section 2, Li-Nong Street, Taipei, Taiwan, Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No-201, Section 2, Shih-Pai Road, Taipei 11217, Taiwan
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Publisher: Portland Press Ltd
Received:
March 09 2000
Revision Received:
June 15 2000
Accepted:
August 02 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (6): 475–482.
Article history
Received:
March 09 2000
Revision Received:
June 15 2000
Accepted:
August 02 2000
Citation
Chi-Jen CHU, Shwu-Ling WU, Fa-Yauh LEE, Sun-Sang WANG, Full-Young CHANG, Han-Chieh LIN, Che-Chang CHAN, Shou-Dong LEE; Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin. Clin Sci (Lond) 1 December 2000; 99 (6): 475–482. doi: https://doi.org/10.1042/cs0990475
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