Peripheral mechanisms involved in the pressor and bradycardic effects of centrally administered arachidonic acid.
In the current study, we aimed to determine the cardiovascular effects of arachidonic acid and peripheral mechanisms mediated these effects in normotensive conscious rats. Studies were performed in male Sprague Dawley rats. Arachidonic acid was injected intracerebroventricularly (i.c.v.) at the doses of 75, 150 or 300 microg and it caused dose- and time-dependent increase in mean arterial pressure and decrease in heart rate in normal conditions. Maximal effects were observed 10 min after 150 and 300 microg dose of arachidonic acid and lasted within 30 min. In order to evaluate the role of main peripheral hormonal mechanisms in those cardiovascular effects, plasma adrenaline, noradrenaline, vasopressin levels and renin activity were measured after arachidonic acid (150 microg; i.c.v.) injection. Centrally injected arachidonic acid increased plasma levels of all these hormones and renin activity. Intravenous pretreatments with prazosin (0.5 mg/kg), an alpha1 adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10 microg/kg), a vasopressin V1 receptor antagonist, or saralasin (250 microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to arachidonic acid (150 microg; i.c.v.) while combined administration of these three antagonists completely abolished the effect. Moreover, both individual and combined antagonist pretreatments fully blocked the bradycardic effect of arachidonic acid. In conclusion, our findings show that centrally administered arachidonic acid increases mean arterial pressure and decreases heart rate in normotensive conscious rats and the increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity appear to mediate the cardiovascular effects of the drug.
Department of Physiology, Faculty of Veterinary Medicine, Uludag University, Gorukle, 16059 Bursa, Turkey.
Cenk
C
Aydin
Murat
M
Yalcin
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology; D014667:Vasopressins / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D006727:Hormone Antagonists; D014667:Vasopressins; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; D012083:Renin; D012504:Saralasin; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine