Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats.

Abstract

BACKGROUND:

Portal hypertension in cirrhosis is the result of increased intrahepatic vascular resistance to portal outflow as well as increased portal tributary blood flow. The angiotensin II type 1 receptor antagonist losartan has been suggested as a portal pressure-lowering drug in patients with cirrhosis.

AIM:

To investigate the systemic and splanchnic haemodynamic effects of different doses of losartan.

METHODS:

In 35 anaesthetized rats with secondary biliary cirrhosis, 3, 10 or 30 mg of losartan kg(-1) or solvent were administered intravenously. Ten sham-operated rats served as controls. Mean arterial pressure and portal pressure were measured by catheters in the femoral artery or portal vein. Systemic and splanchnic haemodynamics and mesenterico-systemic shunt rate were determined by the coloured microsphere method.

RESULTS:

Losartan reduced portal pressure (sham: 9.1 +/- 0.4. cirrhosis: 19.3 +/- 1.1, after 3 mg kg(-1) of losartan 16.4 +/- 0.4, after 10 mg kg(-1) of losartan 15.6 +/- 0.6, after 30 mg kg(-1) of losartan 14.9 +/- 0.6 mmHg) without reducing portal sinusoidal resistance. However, in cirrhotic rats it reduced portal tributary blood flow (sham: 4.3 +/- 0.6. cirrhosis: 8.6 +/- 1.4, after 3 mg kg(-1) of losartan 3.8 +/- 0.7, after 10 mg kg(-1) of losartan 4.7 +/- 0.5, after 30 mg kg(-1) of losartan 5.9 +/- 0.9 mmHg). This was owing either to an increase in splanchnic vascular resistance at the 3 mg kg(-1) dose or to a reduction in the splanchnic perfusion-pressure gradient secondary to a reduction in mean arterial pressure at the 10 and 30 mg kg(-1) doses (mean arterial pressure: sham: 109.7 +/- 4.8. cirrhosis: 109.4 +/- 2.8, after 3 mg kg(-1) of losartan 99.7 +/- 2.9, after 10 mg kg(-1) of losartan 89.9 +/- 3.4, after 30 mg kg(-1) of losartan 81.0 +/- 2.9 mmHg).

CONCLUSIONS:

Low doses of losartan reduce portal hypertension by an increase in splanchnic vascular resistance without hypotensive side-effects on arterial pressure.

• Authors: J Heller, T Shiozawa, J Trebicka, M Hennenberg, M Schepke, M Neef, T Sauerbruch
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 33 Issue 11 Pg. 1006-12 (Nov 2003) ISSN: 0014-2972 [Print] England
• PMID: 14636305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• Losartan

Topics

• Angiotensin II Type 1 Receptor Blockers
• Animals
• Antihypertensive Agents (therapeutic use)
• Blood Pressure (drug effects)
• Cardiac Output (drug effects)
• Hemodynamics (drug effects)
• Hypertension, Portal (drug therapy, etiology, physiopathology)
• Liver Cirrhosis, Experimental (complications, physiopathology)
• Losartan (therapeutic use)
• Male
• Microspheres
• Portal Pressure (drug effects)
• Rats
• Rats, Sprague-Dawley
• Splanchnic Circulation (drug effects)
• Vascular Resistance (drug effects)