Hypotensive effects of 8-hydroxy-2-(di-n-propylamino)tetralin and 5-methylurapidil following stereotaxic microinjection into the ventral medulla of the rat

Abstract

1. The effects of the 5-HT1a receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 5-methylurapidil (5-MU) on blood pressure and heart rate were investigated in the anaesthetized normotensive rat after local injection into the ventral medulla (medial part of the area of the B1/B3 cell group). 2. Both 8-OH-DPAT and 5-MU, decreased arterial blood pressure and heart rate. Local injection of the alpha 1-adrenoceptor antagonist prazosin did not affect cardiovascular parameters. 3. Subcutaneous injection of the 5-HT1a receptor antagonists spiroxatrine or spiperone inhibited the cardiovascular response to 8-OH-DPAT and 5-MU. 4. Histological examination showed the injection sites which were associated with cardiovascular responses to the agonists to be contained within the medial part of the area of the B1/B3 cell group, corresponding to the region of the nucleus raphe magnus and pallidus. Injections of agonists into adjacent areas had no effect on blood pressure or heart rate. 5. The results support the hypothesis that activation of somatodendritic 5-HT1a autoreceptors located on 5-hydroxytryptaminergic neurones in the ventral medulla of the rat results in a decrease in blood pressure and heart rate. The region of the B1/B3 cell group is suggested as a possible site for the hypotensive action of 5-HT1a receptor agonists.