EFFECTS OF ALPHA-1-ADRENERGIC AND BETA-ADRENERGIC ANTAGONISTS AND 5-HYDROXYTRYPTAMINE RECEPTOR ANTAGONIST ON PORTAL-SYSTEMIC COLLATERAL VASCULAR-RESISTANCE IN CONSCIOUS RATS WITH PORTAL-HYPERTENSION

In order to study the acute effects of pharmacological agents on the vascular resistance of portal-systemic collaterals, a model of total portal vein occlusion with 100% portal-systemic shunts was developed in the conscious rat. The haemodynamic effects of several vaso-active substances were evaluated in this model and compared with those obtained after saline administration. Prazosin (0.5 mg), an alpha1-adrenergic antagonist, significantly reduced mean arterial pressure by 29%, portal pressure from 13.8 +/- 1.0 (mean +/- s.e.m.) to 10.1 +/- 0.4 mmHg and portal tributary blood flow (radioactive microspheres) from 13.6 +/- 2. 1 to 11.7 +/- 1.2 mL/min. It also decreased portal-systemic vascular resistance from 95 +/- 16 to 73 +/- 9 dyn s/cm5 x 10(3). propranolol (4 mg), a beta-adrenergic antagonist, significantly reduced mean arterial pressure by 12% and portal pressure from 15.5 +/- 1.2 to 13.3 +/- 0.9 mmHg while reducing portal tributary blood flow from 14.6 +/- 1.5 to 11.0 +/- 1.7 mL/min and increasing portal systemic collateral vascular resistance from 88 +/- 7 to 103 +/- 8 dyn s/cm5 x 10(3). Ketanserin (0.25 mg/kg), a 5-hydroxytryptamine receptor antagonist, reduced portal pressure from 15.8 +/- 1.0 to 13.3 +/- 0.7 mmHg at a dose that did not alter mean arterial pressure or portal tributary blood flow. It achieved this by reducing portal-systemic collateral vascular resistance from 90 +/- 14 to 74 +/- 13 dyn s/cm5 x 10(3). Saline had no significant effect on systemic and splanchnic haemodynamics. This study shows that ketanserin decreases vascular resistance of portal-systemic collaterals while propranolol increases it. Thus, it is suggested that collateral vascular resistance is accessible to pharmacological manipulation.