Acute effects of sublingual nitroglycerin on cardiovagal and sympathetic baroreflex sensitivity

Abstract

The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd-6th min (post A), and 7th-10th min (post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased significantly (post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly (post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat^-1·mmHg^-1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings.

Keywords: baroreflex sensitivity; muscle sympathetic nerve activity; nitrate.

Figure 1.

A: block diagram of the timeline for the protocol. B: representative recordings of beat-to-beat heart rate (HR), integrated muscle sympathetic nerve activity (MSNA), and blood pressure (BP). MSNA clearly increased 2 min after nitroglycerin (GTN) administration.

Figure 2.

The average values in heart rate (HR; A), systolic blood pressure (SBP; B), diastolic blood pressure (DBP; C), burst frequency (BF; D), burst incidence (BI; E), total muscle sympathetic nerve activity (MSNA; F), and burst area (G) during each period. Small symbols represent individual data (subject number n = 10). Bars represent the average value of each period. P (all): P value for the effect of time on the whole trial by linear mixed-effects model (covariate; age and BMI). *P < 0.05 compared with baseline by linear mixed-effects model. BMI, body mass index.

Figure 3.

The slope of CBRS-all (A), SBRS-BI (B), SBRS-total MSNA (C), and SBRS-burst area (D). Small symbols represent individual data. Bars represent the average value of each period. n = 10 for CBRS, SBRS-BI, and SBRS-total MSNA analysis. In SBRS-burst area analysis, n = 5 for baseline, n = 7 for post A, and n = 9 for post B, others were excluded by their R value < 0.5. In CBRS analysis, age, BMI, and SBP were used as a covariate in linear mixed-effects model for the effect of time. In SBRS analysis, age, BMI, and DBP were used as a covariate. P (all): P value for the effect of time on the whole trial by linear mixed effects model. *P < 0.05 compared with baseline by linear mixed-effects model; n, number of subjects. BI, burst incidence; BMI, body mass index; CBRS, cardiovagal baroreflex sensitivity; DBP, diastolic blood pressure; MSNA, muscle sympathetic nerve activity; SBRS, sympathetic baroreflex sensitivity.

Figure 4.

Representative data of the relationship between DBP and BI (left) or DBP and total MSNA (right). Operating point, point on the regression line corresponding to the averaged diastolic pressure of the subject. BI, burst incidence; BRS, baroreflex sensitivity; DBP, diastolic blood pressure.

Figure 5.

The proportion of DBP falling beats over all beats (%) in all sequences (A), number of DBP falling beats per minute (beats/min; B), DBP falling rate in DBP falling sequences (mmHg/s; C), number of DBP falling sequences per minute (number/min; D), and number of falling beats per DBP falling sequence (E); small symbols represent individual data. Bars represent the average value of each period. DBP, diastolic blood pressure; P (all): P value for the effect of time on the whole trial by linear mixed-effects model. *P < 0.05 compared with baseline by linear mixed-effects model (covariate; age, and BMI); n = 10 subjects.