Both α₁ and α₂‐adrenoceptors mediate the cardiovascular responses to noradrenaline microinjected into the bed nucleus of the stria terminal of rats

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 a 1 -adrenoceptor antagonist WB4101, the a 2 -adrenoceptor antagonist RX821002, the combination of WB4101 and RX821002, the non-selective b-adrenoceptor antagonist propranolol, the selective b 1 -adrenoceptor antagonist CGP20712 or the selective b 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 a 1 and a 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 b 1 -adrenoceptors in the cardiovascular response to noradrenaline microinjected into the BST.

Role of the bed nucleus of the stria terminalis in the cardiovascular responses to acute restraint stress in rats

“…Microinjection of noradrenaline or carbachol into the BST evokes a BP increase associated with reflex bradycardia in unanesthetized rats Crestani et al 2007Crestani et al , 2008. Previous work also pointed to an inhibitory role of the BST on the parasympathetic component of the baroreflex (Crestani et al 2006).…”

“…Rats were divided into eight experimental groups: (1) untreated group, with no guide cannula in the brain; (2) aCSF group, vehicle microinjected in the BST (100 nl); (3) cobalt group, non-selective synaptic inhibitor CoCl 2 (0.1 nmol/100 nl; Crestani et al 2006;Scopinho et al 2007) microinjected in the BST; (4) WB4101 group, selective a 1 -adrenoceptor antagonist WB4101 (15 nmol/100 nl; Crestani et al 2008) microinjected in the BST; (5) RX821002 group, selective a 2 -adrenoceptor antagonist RX821002 (15 nmol/100 nl; Crestani et al 2008) microinjected in the BST; (6) propranolol group, non-selective badrenoceptor antagonist propranolol (15 nmol/100 nl; Crestani et al 2008) microinjected in the BST; (7) homatropine þ aCSF group, aCSF microinjection into the BST after intravenous pretreatment with the cholinergic muscarinic receptor antagonist homatropine methyl bromide (0.2 mg/kg; Tavares and Corrêa 2006), and (8) homatropine þ WB4101 group, WB4101 microinjection into the BST after intravenous pretreatment with homatropine methyl bromide.…”

Noradrenergic neurotransmission within the bed nucleus of the stria terminalis modulates the retention of immobility in the rat forced swimming test

“…Finally, the fourth group received injections of vehicle (n = 9) or ICI118,551 (5, 10, and 15 nmol; n = 6-9/dose). The doses were chosen on the basis of previous studies that involved the use of intra-BNST injections (Crestani et al, 2008). To control for possible nonspecific drug effects on locomotor activity that could interfere with the results of FST, independent groups of animals were subjected to the open field test.…”

Efeitos cardiovasculares causados pela microinjeção de angiotensina II no córtex pré-límbico de ratos

“…Crestani e colaboradores (2008) observaram que as respostas cardiovasculares evocadas pela administração de noradrenalina no núcleo leito da estria terminal (NLET) eram mediadas por um mecanismo sinérgico entre os receptores α1 e α2 adrenérgicos; o bloqueio seletivo dos receptores α1 ou α2 adrenérgicos separadamente bloqueava parcialmente a resposta desencadeada pela noradrenalina nesse núcleo, porém, o bloqueio pleno era observado quando era administrada a combinação de WB4101 (antagonista de receptores α1-adrenérgicos) e RX821002 (antagonista de receptores α2-adrenérgicos), (CRESTANI et al, 2008). , 1984).…”