THE RESPONSE TO ARACHIDONIC-ACID BEFORE AND AFTER NONSTEROIDAL ANTIINFLAMMATORY DRUGS IN NORMOTENSIVE AND HYPERTENSIVE RATS

Objective: To establish equivalent doses of four non-steroidal anti-in flammatory drugs (NSAID) in normotensive and hypertensive rats using i nhibition of the fall in blood pressure produced by the injection of a rachidonic acid as the measure of equivalence. Design: An experimental study using two rat models of hypertension and their normotensive con trols. Methods: Two rat models of hypertension (spontaneously hyperten sive rats and two-kidney, one clip rats) and their normotensive contro ls were studied. The change in blood pressure after intravenous inject ion of arachidonic acid was measured in anaesthetized rats. Blood pres sure was measured from a carotid artery cannula, attached to a pen-rec order. Dose-response curves for the effect of arachidonic acid were es tablished in each type of rat, then the effects of different doses of four NSAID (indomethacin, piroxicam, naproxen and sulindac) on these r esponses were measured. Results: Arachidonic acid produced a dose-depe ndent fall in blood pressure in all rats. However, both types of hyper tensive rats sustained a larger fall in blood pressure for a given dos e of arachidonic acid than did the normotensive controls. Doses of NSA ID were found that inhibited this response in Wistar rats. However, th e doses of NSAID that were equivalent in normotensive rats were not eq uivalent in either type of hypertensive rat; indomethacin had a greate r inhibitory effect. As far as could be established, this was not due to differences in the metabolism of the NSAlD between normotensive and hypertensive rats. Conclusions: The arachidonic acid response can be used as a method of establishing equivalent doses of NSAID in normoten sive and hypertensive rats. Hypertensive rats appear to be more sensit ive to the effects of arachidonic acid than normotensive rats, indepen dent of the model of hypertension. Doses of NSAID that are equivalent in normotensive rats are not equivalent in hypertensive rats. Indometh acin is more effective in attenuating the effect of arachidonic acid, possibly due to actions other than inhibition of cyclo-oxygenase.