Hirose M, Furukawa Y, Kurogouchi F, Nakajima K, Miyashita Y, Chiba S
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
J Pharmacol Exp Ther. 1998 Jul;286(1):70-6.
There are no available data on the direct effect of C-type natriuretic peptide (CNP) and brain natriuretic peptide (BNP) on the myocardial contractility in mammalian hearts. Thus we studied the inotropic and chronotropic effects of CNP-22 and BNP-32 compared with those of atrial natriuretic peptide (ANP)-28 using the isolated, blood-perfused canine right atrial or left ventricular preparations. CNP increased the atrial contractile force in a dose-dependent manner with a small increase in sinus rate in isolated atria, whereas neither ANP nor BNP changed atrial force and rate. CNP but not BNP also increased the ventricular contractile force in isolated ventricles. Pretreatment with a high dose (3 nmol) of CNP attenuated the positive inotropic response to CNP at a low dose (1 nmol) but not to norepinephrine. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the increases in atrial contractile force and sinus rate in response to CNP, but it did not affect the positive cardiac responses to norepinephrine. Propranolol did not block the positive cardiac responses to CNP. 3-Isobutyl-1-methylxanthine in rates of 0.6 to 1.3 mumol/ min attenuated the CNP-induced positive inotropic responses, when it potentiated the positive inotropic response to norepinephrine. On the other hand, parasympathetic nerve stimulation attenuated the positive cardiac responses to CNP and norepinephrine. These results demonstrate that CNP increases myocardial contractile force with a small increase in sinus rate mediated by guanylyl cyclase-linked natriuretic peptide receptors, probably type B receptors in the dog heart, and suggest that the positive inotropic response to CNP is influenced by the cyclic adenosine 3',5'-monophosphate-dependent signal transduction.
关于C型利钠肽（CNP）和脑利钠肽（BNP）对哺乳动物心脏心肌收缩力的直接影响，目前尚无可用数据。因此，我们使用离体、血液灌注的犬右心房或左心室标本，研究了CNP-22和BNP-32与心房利钠肽（ANP）-28相比的变力性和变时性作用。CNP以剂量依赖性方式增加离体心房的收缩力，同时窦性心率略有增加，而ANP和BNP均未改变心房的力量和心率。CNP而非BNP也增加了离体心室的收缩力。高剂量（3 nmol）的CNP预处理减弱了低剂量（1 nmol）CNP的正性变力反应，但对去甲肾上腺素的反应没有影响。一种鸟苷酸环化酶连接的利钠肽受体拮抗剂HS-142-1抑制了CNP引起的心房收缩力增加和窦性心率增加，但不影响对去甲肾上腺素的阳性心脏反应。普萘洛尔不阻断对CNP的阳性心脏反应。当0.6至1.3 μmol/min的3-异丁基-1-甲基黄嘌呤增强对去甲肾上腺素的正性变力反应时，它减弱了CNP诱导的正性变力反应。另一方面，副交感神经刺激减弱了对CNP和去甲肾上腺素的阳性心脏反应。这些结果表明，CNP通过鸟苷酸环化酶连接的利钠肽受体（可能是犬心脏中的B型受体）介导，增加心肌收缩力并使窦性心率略有增加，并表明对CNP的正性变力反应受环磷酸腺苷依赖性信号转导的影响。
