Busnardo Cristiane, Tavares Rodrigo Fiacadori, Corrêa Fernando Morgan Aguiar
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, 14090-090, Brazil.
Auton Neurosci. 2009 Jan 28;145(1-2):63-70. doi: 10.1016/j.autneu.2008.11.005. Epub 2008 Dec 6.
We report on the cardiovascular effects of noradrenaline (NA) microinjection into the hypothalamic supraoptic nucleus (SON) as well as the central and peripheral mechanisms involved in their mediation. Microinjections of NA 1, 3, 10, 30 or 45 nmol/100 nL into the SON caused dose-related pressor and bradycardiac response in unanesthetized rats. The response to NA 10 nmol was blocked by SON pretreatment with 15 nmol of the alpha(2)-adrenoceptor antagonist RX821002 and not affected by pretreatment with equimolar dose of the selective alpha(1)-adrenoceptor antagonist WB4101, suggesting that local alpha(2)-adrenoceptors mediate these responses. Pretreatment of the SON with the nonselective beta-adrenoceptor antagonist propranolol 15 nmol did not affect the pressor response to NA microinjection of into the SON. Moreover, the microinjection of the 100 nmol of the selective alpha(1)-adrenoceptor agonist methoxamine (MET) into the SON did not cause cardiovascular response while the microinjection of the selective alpha(2)-adrenoceptor agonists BHT920 (BHT, 100 nmol) or clonidine (CLO, 5 nmol) caused pressor and bradycardiac responses, similar to that observed after the microinjection of NA. The pressor response to NA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V(1)-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP, suggesting an involvement of circulating vasopressin in this response. In conclusion, our results suggest that pressor responses caused by microinjections of NA into the SON involve activation of local alpha(2)-adrenoceptor receptors and are mediated by vasopressin release into circulation.
我们报告了去甲肾上腺素（NA）微量注射到下丘脑视上核（SON）的心血管效应，以及介导这些效应的中枢和外周机制。向未麻醉大鼠的SON中微量注射1、3、10、30或45 nmol/100 nL的NA会引起剂量相关的升压和心动过缓反应。用15 nmol的α(2)-肾上腺素能受体拮抗剂RX821002预处理SON可阻断对10 nmol NA的反应，而等摩尔剂量的选择性α(1)-肾上腺素能受体拮抗剂WB4101预处理则无影响，这表明局部α(2)-肾上腺素能受体介导了这些反应。用15 nmol非选择性β-肾上腺素能受体拮抗剂普萘洛尔预处理SON不影响对微量注射到SON中的NA的升压反应。此外，向SON中微量注射100 nmol选择性α(1)-肾上腺素能受体激动剂甲氧明（MET）不会引起心血管反应，但微量注射选择性α(2)-肾上腺素能受体激动剂BHT920（BHT，100 nmol）或可乐定（CLO，5 nmol）会引起升压和心动过缓反应，类似于微量注射NA后观察到的反应。静脉注射神经节阻滞剂潘托铵预处理可增强对NA的升压反应，而静脉注射V(1)-血管加压素受体拮抗剂dTyr(CH2)5(Me)AVP预处理可阻断该反应，这表明循环血管加压素参与了该反应。总之，我们的结果表明，向SON中微量注射NA引起的升压反应涉及局部α(2)-肾上腺素能受体的激活，并由血管加压素释放到循环中介导。
