Yuan Kuichang, Rhee Kyoung-Suk, Park Woo Hyun, Kim Soo Wan, Kim Suhn Hee
Department of Physiology, Medical School, Chonbuk National University, Jeonju 561-180, Republic of Korea.
Peptides. 2008 Jul;29(7):1207-15. doi: 10.1016/j.peptides.2008.02.011. Epub 2008 Feb 26.
Sympathetic nervous system and atrial natriuretic peptide (ANP) system play fundamental roles in the regulation of cardiovascular functions. Overactivity of sympathetic nervous system can lead into cardiovascular diseases such as heart failure and hypertension. The present study aimed to define which adrenergic receptors (ARs) affect atrial contractility and ANP release and to determine their modification in renal hypertensive rat atria. An alpha(1)-AR agonist, cirazoline increased ANP release with positive inotropism. These alpha(1)-AR agonist-mediated responses were attenuated by the alpha(1A)-AR antagonist, but not by the alpha(1B)- or alpha(1D)-AR antagonist. An alpha(2)-AR agonist, guanabenz and clonidine increased ANP release with negative inotropism and decreased cAMP level. The order of potency for the increased ANP release was cirazoline>>phenylephrine=guanabenz>>clonidine. In contrast, a beta-AR agonist, isoproterenol decreased ANP release with positive inotropism and these responses were blocked by the beta(1)-AR antagonist but not by the beta(2)-AR antagonist. The increased cAMP level by isoproterenol was suppressed by pretreatment with both beta(1)- and beta(2)-AR antagonists. In renal hypertensive rat atria, the effects of isoproterenol on atrial contractility, ANP release, and cAMP level were attenuated whereas the effect of cirazoline on ANP release was unaltered. Atrial beta(1)-AR mRNA level but not alpha(1A)-AR mRNA level was decreased in renal hypertensive rats. These findings suggest that alpha(1A)- and beta(1)-AR oppositely regulate atrial ANP release and that atrial beta(1)-AR expression/function is impaired in renal hypertensive rats.
交感神经系统和心房利钠肽（ANP）系统在心血管功能调节中发挥着重要作用。交感神经系统过度活跃可导致诸如心力衰竭和高血压等心血管疾病。本研究旨在确定哪些肾上腺素能受体（ARs）影响心房收缩力和ANP释放，并确定它们在肾性高血压大鼠心房中的变化。α(1)-AR激动剂西拉唑啉可增加ANP释放并具有正性肌力作用。这些α(1)-AR激动剂介导的反应被α(1A)-AR拮抗剂减弱，但未被α(1B)-或α(1D)-AR拮抗剂减弱。α(2)-AR激动剂胍那苄和可乐定可增加ANP释放并具有负性肌力作用，同时降低cAMP水平。增加ANP释放的效力顺序为西拉唑啉>>去氧肾上腺素=胍那苄>>异丙肾上腺素。相反，β-AR激动剂异丙肾上腺素可降低ANP释放并具有正性肌力作用，这些反应被β(1)-AR拮抗剂阻断，但未被β(2)-AR拮抗剂阻断。异丙肾上腺素增加的cAMP水平被β(1)-和β(2)-AR拮抗剂预处理所抑制。在肾性高血压大鼠心房中，异丙肾上腺素对心房收缩力、ANP释放和cAMP水平的作用减弱，而西拉唑啉对ANP释放的作用未改变。肾性高血压大鼠心房中β(1)-AR mRNA水平降低，但α(1A)-AR mRNA水平未降低。这些发现表明，α(1A)-和β(1)-AR对心房ANP释放具有相反的调节作用，并且肾性高血压大鼠心房中β(1)-AR的表达/功能受损。
