CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTEREDARACHIDONIC ACID IN HAEMORRHAGE-INDUCED HYPOTENSIVERATS: INVESTIGATION OF A PERIPHERAL MECHANISM

摘要

1. The aims of the present study were to determine the cardiovascular effects of arachidonic acid (AA) and to investigate the peripheral mechanisms mediating these effects in haemorrhage-induced hypotensive rats.2. Acute haemorrhage was induced by withdrawing a total volume of 2.2 mL blood/100 g bodyweight over a period of 10 min. Rats were then injected with 75-300 (mu)-g, i.c.v., A_A and cardiovascular changes were monitored over the next 60 min. Plasma catecholamine and vasopressin levels, as well as plasma renin activity (PRA), were measured 10 min after injection of 150 (mu)g A_A in haemorrhage-induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V1 receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropiony,O-Me-Tyr,Arg~8]-vasopressin (10 (mu)g/kg, i.v.), the ctj-adrenoceptor antagonist prazosin (500 (mu)g/kg, i.v.), the non-specific angiotensin II receptor antagonist saralasin (250 (mu)g/kg, i.v.) or a combination of these three antagonists 5 min before injection of A_A (150 (mu)g, i.c.v.). The effects of these antagonists on responses to A_A were determined.3. Arachidonic acid caused dose- and time-dependent increases in mean arterial pressure and heart rate and reversed hypotension in haemorrhaged rats. Haemorrhage itself produced an increase in plasma catecholamine and vasopressin levels, as well as PRA; injection of A_A produced further increases in these parameters, ranging from 39-123%, under hypotensive conditions. Under hypotensive conditions, pretreatment of rats with all three receptor antagonists produced similar partial blockade of the pressor response to AA, but not the increase in heart rate. Moreover, combined administration of all three receptor antagonists prior to the i.c.v. injection of 150 (mu)g A_A completely abolished the pressor response to A_A in haemorrhage-induced hypotensive rats.4. These results indicate that centrally administered A_A reverses hypotension by increasing blood pressure and heart rate in the hypotensive setting. The observed increases in plasma catecholamine and vasopressin levels, as well as PRA, mediate the pressor response to A_A in haemorrhage-induced hypotensive rats.