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CARDIOVASCULAR EFFECTS OF CENTRALLY ADMINISTERED ARACHIDONIC ACID IN HAEMORRHAGE‐INDUCED HYPOTENSIVE RATS: INVESTIGATION OF A PERIPHERAL MECHANISM
Author(s) -
Yalcin Murat,
Aydin Cenk
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05087.x
Subject(s) - vasopressin , endocrinology , medicine , arachidonic acid , antagonist , saralasin , angiotensin ii , plasma renin activity , prazosin , catecholamine , chemistry , receptor antagonist , blood pressure , renin–angiotensin system , pharmacology , receptor , biochemistry , enzyme
SUMMARY1 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 µg, 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 µg 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 [β‐mercapto‐β,β‐cyclopentamethylenepropionyl 1 , O ‐Me‐Tyr 2 ,Arg 8 ]‐vasopressin (10 µg/kg, i.v.), the α 1 ‐adrenoceptor antagonist prazosin (500 µg/kg, i.v.), the non‐specific angiotensin II receptor antagonist saralasin (250 µg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 µg, 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 µg 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.