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. 2008 Feb;153(3):583-90.
doi: 10.1038/sj.bjp.0707591. Epub 2007 Nov 26.

Both alpha1 and alpha2-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the bed nucleus of the stria terminal of rats

C C Crestani  1 , F H F Alves, L B Resstel, F M A Corrêa
Affiliations

Both alpha1 and alpha2-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the bed nucleus of the stria terminal of rats

C C Crestani et al. Br J Pharmacol. 2008 Feb.

Abstract

Background and purpose: We have previously shown that noradrenaline microinjected into the bed nucleus of stria terminalis (BST) elicited pressor and bradycardiac responses in unanaesthetized rats. In the present study, we investigated the subtype of adrenoceptors that mediates the cardiovascular response to noradrenaline microinjection into the BST.

Experimental approach: Cardiovascular responses following noradrenaline microinjection into the BST of male Wistar rats were studied before and after BST pretreatment with different doses of the selective alpha(1)-adrenoceptor antagonist WB4101, the alpha(2)-adrenoceptor antagonist RX821002, the combination of WB4101 and RX821002, the non-selective beta-adrenoceptor antagonist propranolol, the selective beta(1)-adrenoceptor antagonist CGP20712 or the selective beta(2)-adrenoceptor antagonist ICI118,551.

Key results: Noradrenaline microinjected into the BST of unanaesthetized rats caused pressor and bradycardiac responses. Pretreatment of the BST with different doses of either WB4101 or RX821002 only partially reduced the response to noradrenaline. However, the response to noradrenaline was blocked when WB4101 and RX821002 were combined. Pretreatment with this combination also shifted the resulting dose-effect curve to the left, clearly showing a potentiating effect of this antagonist combination. Pretreatment with different doses of either propranolol or CGP20712 increased the cardiovascular responses to noradrenaline microinjected into the BST. Pretreatment with ICI118,551 did not affect cardiovascular responses to noradrenaline.

Conclusion and implications: The present results indicate that alpha(1) and alpha(2)-adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the BST. In addition, they point to an inhibitory role played by the activation of local beta(1)-adrenoceptors in the cardiovascular response to noradrenaline microinjected into the BST.

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Figures

Figure 1
Figure 1
Inhibition of MAP and HR responses (expressed as %) to the microinjection of noradrenaline (10 nmol 100 nl−1) into the BST after pretreatment of the BST with different doses of the α1-adrenoceptor antagonist WB4101 (10, 15 and 25 nmol; n=4 for each dose), the α2-adrenoceptor antagonist RX821002 (10, 15 and 25 nmol; n=4 for each dose) and WB4101+RX821002 (5, 10, 15 and 25 nmol of each drug; n=3 for 5 nmol and n=4 for the other doses). Curves were generated by nonlinear regression analysis. Symbols represent means and vertical lines indicate the s.e.mean. BST, bed nucleus of stria terminalis; HR, heart rate; MAP=mean arterial pressure.
Figure 2
Figure 2
Typical recordings showing MAP, PAP and HR changes in response to noradrenaline (10 nmol 100 nl−1) microinjected into the BST before and after pretreatment of the BST in different animals with WB4101 (25 nmol), RX821002 (25 nmol) or WB4101+RX821002 (25 nmol). BST, bed nucleus of stria terminalis; HR, heart rate; MAP, mean arterial pressure; PAP, pulsatile arterial pressure.
Figure 3
Figure 3
Increase of MAP and HR responses (expressed as %) to noradrenaline (10 nmol 100 nl−1) microinjected into the BST caused by pretreatment of the BST with different doses of the nonselective β-adrenoceptor antagonist propranolol (2.5, 7.5 or 12.5 nmol; n=4 for each dose), the selective β2-adrenoceptor antagonist ICI118,552 (2.5, 7.5 or 12.5 nmol; n=4 for each dose) or the selective β1-adrenoceptor antagonist CGP20712 (2.5, 7.5 or 12.5 nmol; n=4 for each dose). Curves were generated by nonlinear regression analysis. Symbols represent means and vertical lines indicate the s.e.mean. BST, bed nucleus of stria terminalis; HR, heart rate; MAP, mean arterial pressure.
Figure 4
Figure 4
Typical recordings showing MAP, PAP and HR changes in response to noradrenaline (10 nmol 100 nl−1) microinjected into the BST before and after BST pretreatment with CGP20712 (12.5 nmol). BST, bed nucleus of stria terminalis; HR, heart rate; MAP, mean arterial pressure; PAP, pulsatile arterial pressure.
Figure 5
Figure 5
Photomicrograph and diagrammatic representation modified from the rat brain atlas of Paxinos and Watson (1997), indicating the sites of microinjection into the BST of all the animals used in the experiments. ac, anterior commissure; f, fornix; IA, interaural; ic, internal capsule; LSV, ventral lateral septal area; LV, lateral ventricle; PS, parastrial; st, stria terminalis.
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