Pressor effects of the alpha 2-adrenoceptor agonist B-HT 933 in anaesthetized and haemorrhagic rats: comparison with the haemodynamic effects of amidephrine. 1989

M R MacLean, and M Thomson, and C R Hiley
Department of Pharmacology, University of Cambridge.

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

UI MeSH Term Description Entries
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001784 Blood Gas Analysis Measurement of oxygen and carbon dioxide in the blood. Analysis, Blood Gas,Analyses, Blood Gas,Blood Gas Analyses,Gas Analyses, Blood,Gas Analysis, Blood
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002302 Cardiac Output The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat). Cardiac Outputs,Output, Cardiac,Outputs, Cardiac
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages

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