Cardiovascular Effects of Centrally Administered Arachidonic Acid in Haemorrhage‐induced Hypotensive Rats: Investigation of a Peripheral Mechanism

Abstract

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 microg, i.c.v., AA 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 microg AA in haemorrhage-induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V(1) receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin (10 microg/kg, i.v.), the alpha(1)-adrenoceptor antagonist prazosin (500 microg/kg, i.v.), the non-specific angiotensin II receptor antagonist saralasin (250 microg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 microg, i.c.v.). The effects of these antagonists on responses to AA 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 AA 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 microg AA completely abolished the pressor response to AA in haemorrhage-induced hypotensive rats. 4. These results indicate that centrally administered AA 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 AA in haemorrhage-induced hypotensive rats.

Effect of Long-Term Centrally Injected Histamine and Its Receptors Antagonist on The Hypothalamic Cyclooxygenase and Lipoxygenase Enzymes in Rats

“…20 It also modulates ion channels and regulates the activity of many enzymes, including protein kinase A, protein kinase C, and NADPH oxidase. 21 Recently we reported that intracerebroventricularly (ICV) administered AA, by activating the central COX pathway, leads to pressor cardiovascular effects in normotensive [22][23][24] and hemorrhaged hypotensive rats, 25,26 had a hyperventilation effect on respiratory system, 27,28 and stimulation of male hypothalamic-pituitary-gonadal axis. 29 We also reported that inhibition of central COX enzyme completely and blockage of central thromboxane A2 synthesis (TXA2) partially prevented AA-evoked pressor, [22][23][24][25][26] hyperventilation 27,28, and neuroendocrine effects.…”

The features of reserpine-induced gastric mucosal lesions

“…In control rats, vehicle (dimethyl sulfoxide, 5 µL) was injected into the lateral cerebral ventricle. The coordinates were 0.9 mm posterior to bregma, 1.6 mm lateral from the midline and 3.7 mm below the surface of the skull [16][17][18][19][20] .…”