Endogenous atrial natriuretic peptide inhibits endothelin-1 secretion in dogs with severe congestive heart failure.
Endogenous atrial natriuretic peptide inhibits endothelin-1 secretion in dogs with severe congestive heart failure.
复制标题
内源性心房钠尿肽抑制严重充血性心力衰竭犬的内皮素-1 分泌。
DOI：
10.1152/ajpheart.1996.270.5.h1819
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
M. Kinoshita
中科院分区：
文献类型：
--
作者：
A. Wada;T. Tsutamato;Y. Maeda;T. Kanamori;Y. Matsuda;M. Kinoshita
心房钠素肽（ANP）已被证明可以抵消内皮素-1 （ET-1）的反应，但内源性ANP是否真的抑制体内ET-1的全身释放尚未确定。我们将鸟苷酸环化酶偶联ANP受体的特异性拮抗剂HS-142-1 （HS）给清醒的右心室快速起搏引起的严重充血性心力衰竭（CHF）犬（n = 5，持续22天），剂量分别为0.3、1.0和3.0 mg/kg，间隔30分钟。在本研究中，与对照组（65 +/- 4,P < 0.01, 1.30 +/- 0.17 pg/ml, P < 0.001）相比，CHF组血浆ANP和ET-1水平显著升高（分别为348 +/-58和4.54 +/- 0.60 pg/ml）。HS抑制血浆鸟苷3′，5′-环单磷酸鸟苷（cGMP）水平呈剂量依赖性，从21.8 +/- 2.2到7.2 +/- 1.4 pmol/ml (P < 0.001)，同时血浆ET-1水平从4.54 +/- 0.60到6.60 +/- 0.72 pg/ml （P < 0.05）。血浆cGMP降低与血浆ET-1升高呈显著负相关（r = -0.64, P < 0.01）。尽管有这些反应，平均动脉压和肺动脉压没有明显变化。血浆血管紧张素II和精氨酸抗利尿素水平也没有明显变化，这两种物质都被报道能刺激体外ET-1的分泌。这些结果强烈提示内源性ANP通过cgmp介导的途径直接抑制内源性ET-1的分泌。
Atrial natriuretic peptide (ANP) has been shown to counteract the response of endothelin-1 (ET-1), but whether endogenous ANP actually inhibits the systemic release of ET-1 in vivo has not yet been determined. We administered HS-142-1 (HS), a specific antagonist of the guanylate cyclase-coupled ANP receptor, to conscious dogs with severe congestive heart failure (CHF) produced by rapid right ventricular pacing (n = 5, for 22 days) at doses of 0.3, 1.0, and 3.0 mg/kg at 30-minutes intervals. In the present study, plasma ANP and ET-1 levels were significantly elevated in CHF(348 +/-58 and 4.54 +/- 0.60 pg/ml, respectively compared with those in control dogs (65 +/- 4, P < 0.01, 1.30 +/- 0.17 pg/ml, P < 0.001). HS inhibited plasma guanosine 3',5'-cyclic monophosphate (cGMP) levels, a biological market of endogenous ANP activity, in a dose-dependent manner from 21.8 +/- 2.2 to 7.2 +/- 1.4 pmol/ml (P < 0.001), with concomitant significant increases in plasma ET-1 levels from 4.54 +/- 0.60 to 6.60 +/- 0.72 pg/ml (P < 0.05). There was a significant negative correlation between the decrease in plasma cGMP and the increment in plasma ET-1 (r = -0.64, P < 0.01). Despite these responses, mean arterial pressure and pulmonary arterial pressure did not change significantly. Plasma angiotensin II and arginine vasopressin levels, both of which have been reported to stimulate ET-1 secretion in vitro, also showed no significant changes. These results strongly suggest that endogenous ANP directly inhibits endogenous ET-1 secretion through a cGMP-mediated pathway in chronic severe CHF.