Sustained increase in arterial blood pressure and vascular resistance induced by infusion of arachidonic acid in rats.

Abstract

The haemodynamic responses to arachidonic acid (AA) have been investigated in seven groups of anaesthetized rats. Sodium arachidonate was infused intravenously for 4 or 20 min, and arterial blood pressure was recorded continuously. Cardiac output and organ blood flow were measured by microspheres. Infusion of arachidonate caused first a fast drop in arterial blood pressure, thereafter it increased steadily for 5-15 min towards a pressure about 25 mmHg above control level. The high pressure was maintained for at least 1 h. Repeated infusions of arachidonate gave similar responses. Inhibition of cyclo-oxygenase by indomethacin prevented the initial pressure drop to arachidonate, but not the sustained increase in pressure. Arterial pressure, total vascular resistance and blood flow in the kidneys, adrenals and spleen were significantly reduced, whereas cardiac output was not changed 4 min after start infusion of arachidonate. However, average blood pressure was significantly increased 22 and 35 min after start infusion (from 103.9 +/- 2.9 to 128.1 +/- 6.1 and 135.8 +/- 4.6 mmHg). Mean vascular resistance increased simultaneously (from 3.5 +/- 0.2 to 4.7 +/- 0.4 and 5.2 +/- 0.4 mmHg 100 mL-1), while cardiac output, stroke volume and heart rate were maintained or slightly reduced. The renal blood flow was significantly lowered (from average 4.9 +/- 0.1 to 3.3 +/- 0.2 and 4.0 +/- 0.2 mL min-1). Indomethacin did not prevent the changes in vascular resistance or organ blood flow recorded after 20-35 min. On the other hand, inhibition of both cyclo-oxygenase, lipoxygenase and the cytochrome P450 pathways by eicosatetrayonic acid (ETYA) normalized all haemodynamic parameters. Likewise, the rise in pressure was prevented by 17-octadecynoic acid (17-ODYA), an inhibitor of the cytochrome P450 enzyme activity. Thus, arachidonate infusion caused a transient decrease, and then a sustained increase in arterial pressure and vascular resistance, and a long-lasting reduction in renal blood flow, possibly owing to release of a cytochrome P450 dependent vasoconstrictor metabolite of AA.