Proceedings of The Physiological Society

University of Leeds (2002) J Physiol 544P, S015

Communications

Enhancement of the baroreceptor-heart rate reflex by nitric oxide in the nucleus ambiguus of anaesthetised rats

J. Fletcher*, W.E. Moody*, S. Chowdhary† and J.H. Coote*

Departments of *Physiology and †Cardiovascular Medicine, University of Birmingham, Birmingham B15 2TT, UK


Nitric oxide (NO) produced within the central nervous system (CNS) blunts the baroreflex control of heart rate. Evidence suggests that this action could be occurring within the nucleus tractus soiltarii (Paton et al. 2001) where the enzyme NO synthase (NOS) has been localised immunohistochemically. However, NOS is also abundant in the nucleus ambiguus (NA) where vagal neurones supplying the heart are situated (Maqbool et al. 1995). There is only one report indicating that NO within the NA may play a role in the vagal control of heart rate and this suggests that cardiac vagal neurones are excited (Ruggeri et al. 2000). No studies have examined how NO in the NA may influence the baroreceptor heart rate reflex. In the present study in fifteen Wistar rats anaesthetised with urethane (650 mg kg-1 I.V.) we sought to determine the influence of NO on vagal tone and the baroreceptor reflex. Using stereotaxic co-ordinates the heart rate response to microinjection (50 nl) of the NO donor sodium nitroprusside (SNP, 1 mM) and the NO synthase (NOS) inhibitor, N G-nitro-L-arginine (L-NNA, 3 mM) into functionally identified cardioinhibitory sites in the NA was determined. To estimate baroreflex sensitivity (BRS), RR interval and mean arterial pressure (MAP) changes were calculated following a bolus injection of phenylephrine hydrochloride (1-2 mg kg-1 I.V.). Data (means ± S.E.M.) were subjected to Student's paired t test (P < 0.05). Rats were humanely killed with an overdose of urethane at the end of the experiment. Unilateral microinjection of SNP in the NA induced a significant decrease in heart rate (-68 ± 14 b.p.m.; P < 0.001), with no significant change in MAP (2 ± 2 mmHg, n = 12 sites). Bilateral NOS inhibition produced a non-significant change in heart rate (+2 ± 1 b.p.m.), with no significant change in MAP (-2 ± 1 mmHg, n = 22 sites). However, bilateral NOS inhibition resulted in a significant attenuation in the slope of the regression line between RR interval and MAP compared with control (0.595 ± 0.095 ms mmHg-1 at control; 0.136 ± 0.046 ms mmHg-1 following L-NNA; P < 0.001, n = 11 sites).

The results confirm that NO within the NA of anaesthetised rats excites cardiac vagal neurones. There appears to be no tonic NO modulation of cardiac vagal motoneurone activity regulating heart rate, as blockade of NO synthesis does not alter resting heart rate. NO at synapses within the NA facilitates the baroreflex control of heart rate.

All procedures accord with current UK legislation.

Where applicable, experiments conform with Society ethical requirements