Tommaso Gori1, John S Floras, John D Parker. 1. Division of Cardiology, Department of Medicine, Mount Sinai Hospital, and the University Health Network Hospitals, Toronto, Canada.
Abstract
OBJECTIVES: We set out to determine the effect of sustained treatment with nitroglycerin (GTN) on neural modulation of heart rate in humans. BACKGROUND: Acutely, exogenous and endogenous nitric oxide reduces sympathetic, while increasing vagal, outflow. An animal study showed loss of these effects during nitrate tolerance. METHODS: A total of 29 healthy men (age range, 18 to 32 years) received transdermal GTN (0.6 mg/h/24 h) or no therapy for six days in a parallel controlled trial. The reflex regulation of heart rate was assessed with the spontaneous baroreflex sensitivity (BRS) method. Heart rate variability was calculated both in time (standard deviation of mean RR interval [RRSD]) and frequency domains (Fast Fourier Transformation) over 10-min intervals. RESULTS: Systolic blood pressure was unchanged after continuous GTN, whereas mean RR interval decreased significantly (from 839 to 781 ms, p < 0.05). Nitroglycerin blunted BRS (p < 0.05). When compared with untreated subjects, RRSD was significantly lower after GTN, whereas the ratio of low to high frequencies was increased (all p < 0.05). CONCLUSIONS: Chronic GTN reduces tonic and reflex vagal heart rate modulation, resulting in greater relative sympathetic influence. Importantly, such changes in the regulation of chronotropic oscillations might have negative prognostic implications in both heart failure and coronary artery disease. Furthermore, because chronic GTN alters the blood pressure/heart rate relationship, our data suggest caution when using these variables as pharmacodynamic markers for the development of nitrate tolerance.
OBJECTIVES: We set out to determine the effect of sustained treatment with nitroglycerin (GTN) on neural modulation of heart rate in humans. BACKGROUND: Acutely, exogenous and endogenous nitric oxide reduces sympathetic, while increasing vagal, outflow. An animal study showed loss of these effects during nitrate tolerance. METHODS: A total of 29 healthy men (age range, 18 to 32 years) received transdermal GTN (0.6 mg/h/24 h) or no therapy for six days in a parallel controlled trial. The reflex regulation of heart rate was assessed with the spontaneous baroreflex sensitivity (BRS) method. Heart rate variability was calculated both in time (standard deviation of mean RR interval [RRSD]) and frequency domains (Fast Fourier Transformation) over 10-min intervals. RESULTS: Systolic blood pressure was unchanged after continuous GTN, whereas mean RR interval decreased significantly (from 839 to 781 ms, p < 0.05). Nitroglycerin blunted BRS (p < 0.05). When compared with untreated subjects, RRSD was significantly lower after GTN, whereas the ratio of low to high frequencies was increased (all p < 0.05). CONCLUSIONS: Chronic GTN reduces tonic and reflex vagal heart rate modulation, resulting in greater relative sympathetic influence. Importantly, such changes in the regulation of chronotropic oscillations might have negative prognostic implications in both heart failure and coronary artery disease. Furthermore, because chronic GTN alters the blood pressure/heart rate relationship, our data suggest caution when using these variables as pharmacodynamic markers for the development of nitrate tolerance.
Authors: Takuto Hamaoka; Cheryl Blaha; Jonathan C Luck; Urs A Leuenberger; Lawrence I Sinoway; Jian Cui Journal: Am J Physiol Regul Integr Comp Physiol Date: 2021-08-11 Impact factor: 3.210
Authors: Sebastian Steven; Matthias Oelze; Michael Hausding; Siyer Roohani; Fatemeh Kashani; Swenja Kröller-Schön; Johanna Helmstädter; Thomas Jansen; Christine Baum; Marc Iglarz; Eberhard Schulz; Thomas Münzel; Andreas Daiber Journal: Oxid Med Cell Longev Date: 2018-12-27 Impact factor: 6.543