Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats

Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats
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DOI:
10.1152/ajpheart.00461.2005
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发表时间:
2006-03-01
影响因子:
4.8
通讯作者:
Abe, Y
Abe, Y
中科院分区:
医学2区
文献类型:
--
作者:
Fujisawa, Y;Nagai, Y;Abe, Y

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最近,降钙素基因相关肽(CGRP)家族的新成员,肾上腺髓质素2(AM 2)或intermedin(IMD),被确定。AM 2/ IMD已显示在小鼠和大鼠中具有血管扩张作用,并对大鼠的尿液形成有影响。在本研究中,我们研究了静脉输注大鼠AM 2(rAM 2)对清醒无束缚大鼠血压(BP),心率(HR),肾交感神经活动(RSNA)和肾血流量(RBF)的影响,相对于大鼠肾上腺髓质素(rAM)和肾上腺髓质素前体NH 2-末端20肽(rPAMP)的影响。静脉输注rAM 2(5 nmol/kg)可显著降低BP,增加HR、RSNA和RBF。20分钟后,这些兴奋和交感神经兴奋作用减弱,停止输注后30分钟,HR恢复至对照水平。相反,在肽输注停止后60分钟,RBF的显著增加仍然明显。rAM(5 nmol/kg)的BP,HR和RSNA反应的持续时间长于rAM 2输注,而rAM 2和rAM诱导的RBF增加的幅度和持续时间相似。rPAMP(200 nmol/kg)可增加HR和RSNA,但对RBF无影响。去压力感受器神经支配抑制但并未减少HR和RSNA相对于rAM 2的增加。这些发现表明rAM 2和rAM的生理作用是相似的,并且rAM 2对肾血管床也具有持久的血管扩张作用。
Recently, a new member of the calcitonin gene-related peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified. AM2/ IMD has been shown to have a vasodilator effect in mice and rats and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA), and renal blood flow (RBF) in conscious unrestrained rats relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin NH2-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA, and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The duration of BP, HR, and RSNA responses was longer with rAM (5 nmol/kg) than with rAM2 infusion, whereas the increases in RBF induced by rAM2 and rAM were similar in their amplitude and duration. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA but had no effect on RBF. Baroreceptor denervation suppressed, but did not diminish, the increases in HR and RSNA to rAM2. These findings indicate that the physiological roles of rAM2 and rAM are similar and that rAM2 also has a long-lasting vasodilator action on the renal vascular bed.