title: Pressor effects of the alpha 2-adrenoceptor agonist B-HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine.
abstract: 1. Blood pressure responses to single and multiple bolus doses of the alpha 2-adrenoceptor agonist B-HT 933 were analysed in intact anaesthetized rats which were either normotensive or hypotensive as a result of haemorrhage. Single bolus doses of B-HT 933 in normotensive rats induced a fall in blood pressure, whilst further doses induced dose-dependent pressor responses which were inhibited by the alpha 2-adrenoceptor antagonist yohimbine and unaffected by the alpha 1-adrenoceptor agonist prazosin. In the haemorrhagic, hypotensive animals, single bolus doses of B-HT 933 induced immediate dose-dependent pressor responses; the maximum pressor responses to the bolus of B-HT 933 and its ED50 values were the same in both the normotensive and hypotensive, haemorrhagic animals. 2. Cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in intact anaesthetized normotensive and haemorrhagic, hypotensive rats during depressor (normotensive) and pressor (normotensive and hypotensive) responses to B-HT 933. Haemodynamics were also determined during pressor responses to the alpha 1-adrenoceptor agonist amidephrine. 3. In control normotensive rats, a single dose of B-HT 933 (1 mg kg-1) reduced blood pressure by reducing cardiac output (through a decrease in heart rate). It increased the fractional distribution of cardiac output to the spleen and stomach, reduced it to the heart and liver and reduced cardiac and hepatic blood flow. A further dose of B-HT 933 (1 mg kg-1 bolus followed by 100 micrograms min-1 infusion) increased blood pressure by increasing total peripheral resistance, which was accompanied by decreased proportions of cardiac output passing to the heart, liver and testes. There was also increased fractional distribution of cardiac output to the lungs, spleen, kidneys and stomach but blood flows through the liver and testes were reduced. Amidephrine (6 micrograms kg-1 bolus followed by 0.5 micrograms min-1 infusion) increased blood pressure by increasing cardiac output through an increased stroke volume. It increased cardiac output distribution to the kidneys and brain, increasing blood flow through the heart, lungs, brain, testes, epididimides, skin and large intestine. 4. Haemorrhage caused a fall in blood pressure which resulted from decreased total peripheral resistance and cardiac output (the latter due to decreases in both heart rate and stroke volume). It reduced the proportion of cardiac output distributed to the lungs, spleen, kidneys, testes and pancreas/mesentery and decreased blood flow through these organs as well as through the heart, liver, brain, epididimides, skin and the gastrointestinal tract.4
authors.affiliation: Department of Pharmacology, University of Cambridge.
authors.forename: M R
authors.initials: MR
authors.lastname: MacLean
authors.forename: M
authors.initials: M
authors.lastname: Thomson
authors.forename: C R
authors.initials: CR
authors.lastname: Hiley
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D004983:Ethanolamines; D014662:Vasoconstrictor Agents; C016980:amidephrine; C015603:azepexole