HYPERDYNAMIC CIRCULATION OF CIRRHOTIC RATS - ROLE OF SUBSTANCE-P AND ITS RELATIONSHIP TO NITRIC-OXIDE

Background: It has been suggested that excessive formation of nitric o xide (NO) is responsible for the hyperdynamic circulation observed in portal hypertension. Substance P is a neuropeptide partly cleared by t he liver and causes vasodilatation through the activation of the endot helial NO pathway. However, there are no previously published data con cerning the plasma level of substance P in cirrhotic rats and its rela tionship to NO. Methods: Plasma concentrations of substance P and nitr ate/nitrite (an index of NO production) were determined in control rat s and cirrhotic rats with or without ascites using an enzyme-linked im mununosorbent assay and a colorimetric assay, respectively. In additio n, systemic and portal hemodynamics were evaluated by a thermodilution technique and catheterization. Results: Cirrhotic rats with and witho ut ascites had a lower systemic vascular resistance (2.6 +/- 0.2 and 3 .9 +/- 0.4 mmHg.ml(-1).min.100 g body weight, respectively) and higher portal pressure (14.6 +/- 0.6 and 11.3 +/- 1.8 mmHg) than control rat s (6.5 +/- 0.3 mmHg.ml(-1).min.100 g BW and 6.8 +/- 0.2 mmHg, respecti vely, P < 0.05), and cirrhotic rats with ascites had the lowest system ic vascular resistance. Plasma levels of nitrate/nitrite progressively increased in relation to the severity of liver dysfunction (control r ats, 2.7 +/- 0.5 nmol/ml; cirrhotic rats without ascites, 5.6 +/- 1.3 nmol/ml; cirrhotic rats with ascites, 8.3 +/- 2.2 nmol/ml; P < 0.05). Cirrhotic rats with ascites displayed higher plasma values of substanc e P (57.7 +/- 5.9 pg/ml) than cirrhotic rats without ascites (37.9 +/- 3.1 pg/ml, P < 0.05) and control rats (30.1 +/- 1.0 pg/ml, P < 0.05). There was no significant difference in plasma substance P values betw een control rats and cirrhotic rats without ascites (P > 0.05). No cor relation was found between plasma levels of substance P and nitrate/ni trite (r = 0.318, P > 0.05). Conclusions: Excessive formation of NO ma y be responsible, at least partly, for the hemodynamic derangements in cirrhosis. Although substance P may not participate in the initiation of a hyperdynamic circulation in cirrhosis, it may contribute to the maintenance of the hyperdynamic circulation observed in cirrhotic rats with ascites.