Acute haemodynamic effects of losartan in anaesthetized cirrhotic rats.
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.


OBJECTIVE
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.
Heller
J
J
Department of Internal Medicine I, University of Bonn, Bonn, Germany. jheller@uni-bonn.de
Shiozawa
T
T
Trebicka
J
J
Hennenberg
M
M
Schepke
M
M
Neef
M
M
Sauerbruch
T
T
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000150:complications* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008863:Microspheres; D017082:Portal Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D019808:Losartan