Direct chronotropic effects of atrial and C‐type natriuretic peptides in anaesthetized dogs

Abstract

1 The chronotropic effects of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) were investigated using injections (50 Mg in 1 ml of Tyrode solution as bolus over 1 min) directly into the sinus node artery of 21 anaesthetized and vagotomized dogs which had been pretreated with a f,-adrenoceptor antagonist. The injections were also repeated following: (a) a-adrenoceptor antagonism (prazosin) and muscarinic receptor antagonism (atropine); (b) inhibition of prostaglandin synthesis (indomethacin); (c) angiotensin II AT1 receptor antagonism (losartan); (d) histamine HI (mepyramine) and H2 (cimetidine) receptor antagonism. 2 The results obtained indicate that ANP had no significant effect on the basal sinus rate, whereas CNP produced a slight but significant increase of 12+2 beats min-'. The effect of CNP was long-lasting (return to pre-injection levels after maximum effect in 17+3 min) and was not influenced by the various antagonists mentioned above. 3 During in vitro experiments on spontaneously beating right atria isolated from 6 dogs, the injection of CNP (50 pg in 1 ml of Tyrode solution) into the sinus node artery produced an increase in atrial rate of 14+1 beats min-'. 4 The results of this work indicate that CNP exerts a significant and prolonged positive chronotropic effect both in vivo and in vitro. Other studies are required to elucidate the mechanism of action of CNP on the heart conduction system, to ascertain the presence of natriuretic peptide receptor B in the region of the sinoatrial node and to determine the role of CNP in the control of heart rate.

The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors

“…These effects were shown to be dependent on activation of NPR-C and were only seen in the presence of a saturating dose (1 μM) of the β-adrenergic receptor (β-AR) agonist isoproterenol (ISO). On the other hand some studies have shown that NPs can increase HR and/or SAN activity in vivo and/or in isolated atrial preparations [12][13][14]. These variable responses may be related to a lack of understanding of how different NPRs contribute to physiological responses in different conditions.…”

Effects of C‐type natriuretic peptide on rat cardiac contractility

“…In the rat and human heart, the three natriuretic receptor mRNAs were found (Nunez et al, 1992). Recently, Beaulieu et al (1996) and Hirose et al (1998) reported, respectively, direct chronotropic and dromotropic eects of CNP on anaesthetized dogs. While some studies show that ANP decreases contractility in isolated cardiomyocytes (Neyses & Vetter, 1989;McCall & Fried, 1990), the role of natriuretic peptides in the regulation of cardiac contractility has not been clearly established.…”

“…In the rat and human heart, the three natriuretic receptor mRNAs were found (Nunez et al ., 1992). Recently, Beaulieu et al . (1996) and Hirose et al .…”

C-type natriuretic peptide inhibits ANP secretion and atrial dynamics in perfused atria: NPR-B-cGMP signaling

“…Recently, a regulatory function of CNP has been recognized in the heart, i.e., CNP-induced positive chronotropic (1,2,14) and inotropic (2,14) effects in the dog heart. The natriuretic peptide family (11,29,46) and their specific receptors (2,8,33) have been demonstrated in the cardiac atria.…”