Vol. 286, Issue 1, 70-76, July 1998

C-Type Natriuretic Peptide Increases Myocardial Contractility and Sinus Rate Mediated by Guanylyl Cyclase-Linked Natriuretic Peptide Receptors in Isolated, Blood-Perfused Dog Heart Preparations¹

Masamichi Hirose, Yasuyuki Furukawa, Fumio Kurogouchi, Koichi Nakajima, Yusuke Miyashita and Shigetoshi Chiba

Department of Pharmacology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan

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 µmol/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.