title: Effects of alpha 1 and beta-adrenergic antagonists and 5-hydroxytryptamine receptor antagonist on portal-systemic collateral vascular resistance in conscious rats with portal hypertension.
abstract: 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 alpha 1-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.
authors.affiliation: Laboratoire d'Hémodynamique Splanchnique, Hôpital Beaujon, Clichy, France.
authors.forename: A
authors.initials: A
authors.lastname: Koshy
authors.forename: T
authors.initials: T
authors.lastname: Sekiyama
authors.forename: A
authors.initials: A
authors.lastname: Hadengue
authors.forename: R
authors.initials: R
authors.lastname: Cerini
authors.forename: A
authors.initials: A
authors.lastname: Braillon
authors.forename: D
authors.initials: D
authors.lastname: Lebrec
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003097:Collateral Circulation / Q000187:drug effects; D006975:Hypertension, Portal / Q000503:physiopathology*; D007650:Ketanserin / Q000494:pharmacology*; D008297:Male; D017082:Portal Pressure / Q000187:drug effects; D011168:Portal System / Q000187:drug effects* / Q000503:physiopathology; D011224:Prazosin / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D007650:Ketanserin; D011433:Propranolol; D011224:Prazosin