Effect of glyceryl trinitrate on brainstem cardiovascular regulation in fully conscious and healthy human subjects

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University of Bristol (2001) J Physiol 536P, S008

Communications: Effect of glyceryl trinitrate on brainstem cardiovascular regulation in fully conscious and healthy human subjects

I.S. Mackenzie, C.M. McEniery, I.B. Wilkinson, P.O.O. Julu* and S. Hansen†

Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, *Peripheral Nerve and Autonomic Unit, Imperial College of Science, Technology and Medicine, Department of Neurology, Central Middlesex Hospital, London and †Department of Clinical Physics, Institute of Neurological Sciences, South Glasgow University Hospitals NHS-Trust, Glasgow, UK

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Glyceryl trinitrate (GTN) relaxes vascular smooth muscle; reducing ventricular after-load by its action on arterioles and pre-load because of increased venous capacity and diminished venous return. However, the effect of GTN on large arteries and brainstem cardiovascular regulation is poorly understood. We studied the effects of GTN on cardiac vagal tone (CVT) and cardiac sensitivity to spontaneous baroreflex (CSB), both of which are continuously regulated in the brainstem.

Six subjects (3 males), mean age 33 years, gave informed consent for the study that was approved by the Local Ethics Committee. Arterial pressure (BP), measured at the radial artery by applanation tonometry (CMB-7000, Colin, Japan), and an ECG were continuously recorded, and analog signals sampled at 200 Hz and stored (Powerlab, ADInstruments, UK). After 20 min supine rest baseline values were recorded (2 min) and sublingual GTN (500 µg) given for 5 min (sampling over the last 2 min). Data were analysed using VaguSoft software (MediFit Diagnostics, UK) to measure beat-by-beat maximum rate of BP rise during ejection periods (dP/dt in mmHg s-1), pre-ejection period (PEP in ms) starting with QRS complex and ending with the initiation of BP rise during systole. An index of CVT was measured continuously from the ECG as previously described (Little et al. 1999) and the CSB was measured from the BP and ECG data (Julu et al. 1996). The means of all measurements before and after GTN were compared (Student’s paired t test).

GTN reduced CVT by 30 % (P < 0.02) from (means ± S.E.M.) 11.7 ± 2.8 to 8.2 ± 1.9 units in the linear vagal scale (Julu, 1992), associated with a significant rise in heart rate from 63 ± 4 to 68 ± 5 beats min-1. However, CSB (9.2 ± 2.2 vs. 8.2 ± 2.1 ms mmHg-1; P > 0.2), dP/dt (581 ± 154 vs. 616 ± 89; P > 0.1) and PEP (239 ± 8 vs. 249 ± 10; P > 0.1) were unaltered by GTN. There was no change in systolic or diastolic BP.

In conclusion, GTN did not affect the ability of the left ventricle to generate optimum blood pressure during systole or the duration of isometric ventricular contraction. However, CVT was reduced by a peripheral action of GTN, as the centrally regulated CSB was not affected. We propose that GTN reduces baroreceptor output for a similar dP/dt, thereby reducing the CVT in our subjects. This may be due to a direct vasorelaxant effect of GTN on the large arteries and/or a reduction in central blood pressure.

    Julu, P.O.O. (1992). Auton. Pharmacol. 12, 109-115.

    Julu, P.O.O., Hansen, S., Barnes, A. & Jamal, G.A. (1996). J. Physiol. 497, 7-8P.

    Little, C.J.L., Julu, P.O.O., Hansen, S. & Reid, S.W.J. (1999). Am. J. Physiol. 276, H758-765.

Where applicable, experiments conform with Society ethical requirements.

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