The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1-15)

It has been shown that galanin plays a role in central cardiovascular regulation. Galanin administered centrally induces an increase of heart rate and a weak vasodepressor response, whereas the N-terminal galanin fragment (1-15) elicits vasopressor effects and tachycardia. Furthermore, it has been shown that galanin-(1-15), but not galanin-(1-29), decreases the baroreceptor reflex sensitivity. Since these data demonstrate that both galanin and its N-terminal fragment (1-15) exert a different modulation on central cardiovascular control, the aim of this work has been to study if the specific galanin receptor antagonist Galanin-(1-12)-Pro-(Ala-Leu)(2)-Ala]-amide (M40) could modulate their cardiovascular actions. Urethane anaesthetized rats were injected intracisternally and the changes in mean arterial pressure and heart rate were monitored. Two doses of M40 alone have been tested for their cardiovascular effects. With the dose of 1.0 nmol, a significant tachycardia was observed (P < 0.001), but 0.1 nmol was ineffective. This suggests a possible agonistic effect for the higher doses of M40. The galanin receptor antagonist M40 at the dose of 0.1 nmol failed to modify the weak vasodepressor effects and tachycardia induced by 3.0 nmol of galanin-(1-29). However, the same dose completely blocked the vasopressor and tachycardic responses elicited by 3.0 nmol of galanin-(1-15). These data show that M40 differentially counteracts the central cardiovascular responses of the galanin fragment and give a functional support for the existence of galanin receptor subtypes within the brainstem. Therefore, the present findings can be explained on the basis that the cardiovascular actions of galanin-(1-29) could be mediated by one type of galanin receptor, whereas a galanin receptor subtype that recognizes N-terminal fragments of galanin may mediate the actions of galanin-(1-15). (C) 2000 Elsevier Science B.V. All rights reserved.