Comparative Biochemistry and Physiology Part A 120 (1998) 391 – 397 The intrinsic rate response of the isolated right atrium of the rat, Rattus noregicus Carolyn J. Barrett, Chris P. Bolter *, Suzanne J. Wilson Department of Physiology and the Neuroscience, Research Centre, Uniersity of Otago, Box 913, Dunedin, New Zealand Received 28 April 1996; received in revised form 12 June 1997; accepted 18 June 1997 Abstract Experiments were performed on rat right atria maintained at 37°C in oxygenated Krebs – Henseleit solution, at a baseline diastolic transmural pressure of 2 mmHg. A step increment in right atrial pressure caused an increase in atrial rate which reached a steady value after 2–3 min (rate response). An 8-mmHg increase in atrial pressure caused an 8% increase in atrial rate (n =9, P 0.01). When the atrial rate was reduced by carbamylcholine, the rate response was augmented. After a 34% reduction in atrial rate, an 8-mmHg increase in atrial pressure increased atrial rate by 51% (n =7, P 0.01). When atrial rate was elevated 71% by isoprenaline, the rate response was reversed (atrial rate decreased 3% following an 8-mmHg increase in atrial pressure; n =7, P 0.01). In another series of experiments, atrial rate was adjusted to a wide range of values by exposure to carbamylcholine and isoprenaline, first applied singly, and then in combination. At any given atrial rate, the rate response was always larger when both agonists were present; this difference was greatest when atrial rate was near the control untreated value. © 1998 Elsevier Science Inc. All rights reserved. Keywords: Cardiac pacemaker; Intrinsic atrial rate; Intrinsic cardiac rate regulation; Right atrial pressure; Sinoatrial node 1. Introduction The cardiac pacemaker can respond directly to changes in atrial or auricular pressure. This mecha- nism of pacemaker control, termed intrinsic cardiac rate regulation, has been observed in a wide range of phyla [4]. Recently, in the rabbit, we have exam- ined the intrinsic rate responses of the intact heart in situ and of the isolated right atrium to changes in right atrial pressure [1,2]. These studies described the responses of the pacemaker both in, and without, the presence of background autonomic nervous activity or equivalent pharmacological stimulation. In the rabbit, intrinsic cardiac rate regulation is markedly enhanced when the pacemaker is slowed by vagal or cholinergic stimulation, and reduced when the pace- maker is exposed to -adrenergic agonists. The rabbit had been chosen for these studies since it had been reported that intrinsic cardiac rate regu- lation was better developed in this species than in several other mammals that had been investigated [3,8]. The rat, Rattus noregicus, another mammal frequently used in laboratory studies, may be a con- venient animal for examining the mechanisms under- lying intrinsic rate regulation and its modulation by the autonomic nervous system. Here, we report ob- servations on intrinsic cardiac rate regulation, made in the isolated right atrial preparation of the rat. In addition to extending observations on intrinsic car- diac rate regulation to another species, we have car- ried out experiments which demonstrate the over-riding influence of cholinergic stimulation on this form of pacemaker control. * Corresponding author. Tel.: +64 3 4797327; fax: +64 3 4797323; e-mail: chris.bolter@stonebow.otago.ac.nz. 1095-6433/98/$19.00 © 1998 Elsevier Science Inc. All rights reserved. PII S1095-6433(98)10077-6