Hemodynamic effects of a combination of clonidine and propranolol in conscious cirrhotic rats

Abstract

The hemodynamic effects of the combination of clonidine and propranolol were studied in conscious rats with portal hypertension owing to secondary biliary cirrhosis. Pressure and blood flow measurements (radioactive microsphere method) were performed in three groups of eight rats before and after drug administration. The combined effects of clonidine (2 micrograms/100 g body wt., i.v.) and propranolol (0.2 mg/min for 10 min) were compared with those observed after administration of either clonidine alone or propranolol alone. The association of clonidine and propranolol induced significant decreases in portal pressure (30%) and portal tributary blood flow (43%), the magnitude of these changes being significantly more marked than that after administration of either clonidine alone (12 and 20%, respectively) or propranolol alone (16 and 17%, respectively). After the combination, no significant change in arterial pressure was observed, but cardiac output significantly decreased and systemic vascular resistance significantly increased. Renal blood flow decreased to a similar extent (40%) in the three groups. These findings indicate that the combination of clonidine and propranolol is more effective for reversing splanchnic hemodynamic changes than clonidine alone or propranolol alone. The additive effects of this association are in agreement with the action of clonidine and propranolol at different levels (central and peripheral) and on different receptors (alpha and beta). It suggests that an increase in sympathetic activity may play a major role in hemodynamic changes observed in experimental cirrhosis.

Systemic and splanchnic hemodynamics following hemorrhage and volume restitution with Haemaccel in portal hypertensive rats: The effect of propranolol

“…We found a decrease in renal blood flow in the propranolol‐treated animals. Although this is in accordance with previous reports, 20 its significance is unknown.…”

Haemodynamic effects of 8‐day octreotide and prazosin administration in portal hypertensive rats

“…Several clinical and animal studies have shown that combination of vasocontrictors and vasodilators does indeed offer additional haemodynamic benefits in reversing portal hypertension or averting side-effects. Combination regimens such as vasopressin plus nitroglycerin [26][27][28], terlipressin plus propranolol [29], vasopressin plus ketanserin [30], octreotide plus nitrates [31], propranolol plus nitroglycerin [32], spironolactone plus nitrates [33], propranolol plus clonidine [34] and propranolol plus ketanserin [35] have been observed to be of benefit. On the other hand, combination regimens such as vasopressin plus clonidine [36], propranolol plus furosemide [37], propranolol plus spironolactone [38], octreotide plus propranolol [20] or octreotide plus prazosin (the present study) did not suggest any benefit.…”

Hemodynamic effects of acute tetrandrine and terlipressin administration on portal hypertensive rats

“…and vasodilators does indeed offer additional hemodynamic benefits in reversing portal hypertension or averting side effects. Combination regimens such as vasopressin plus nitroglycerin (Groszmann et al 1982;Tsai et al 1986;Gimson et al 1986), terlipressin plus propranolol (Vachiery et al 1996), vasopressin plus ketanserin (Lee et al 1992), octreotide plus nitrates (Hori et al 1994), propranolol plus nitroglycerin (Kroeger and Groszmann 1985), spironolactone plus nitrates (van de Casteele et al 1996), propranolol plus clonidine (Roulot et al 1989), and propranolol plus ketanserin (Hadengue et al 1989), have been observed to be of benefit. On the other hand, combination regimens such as vasopressin plus clonidine , propranolol plus furosemide (Sogni et al 1994), or propranolol plus spironolactone (Oberti et al 1997) did not suggest benefit.…”