Effects of nitroglycerin-induced vasodilation on elastic and muscular artery stiffness in older Veterans

Abstract

Vascular smooth muscle tone may play an important role in the physiology of increased arterial stiffness that occurs with aging. This study evaluated the impact of smooth muscle tone on arterial stiffness in older individuals following nitroglycerin-induced vasodilation in elastic and muscular arteries. Forty older Veterans (≥60 years old) without known cardiovascular disease were included in this study. Twenty Veterans were included as hypertensive participants (70.8 ± 6.6 years, 10 females), and 20 were included as normotensive controls (72.0 ± 9.3 years, 8 females). Nitroglycerin (NTG)-induced changes in arterial stiffness were measured locally with vascular ultrasound in the carotid and brachial arteries and regionally by carotid-femoral pulse wave velocity (cfPWV) with tonometry. With NTG treatment, both hypertensive participants and normotensive controls Veterans showed increased carotid PWV (6.4 ± 1.3 m/s to 7.2 ± 1.4 m/s, Δ 0.8 ± 1.1 m/s, p = 0.007) and cfPWV (8.6 ± 1.9 m/s to 9.5 ± 2.4 m/s, Δ 0.9 ± 2.3 m/s, p = 0.020) but did not show changes in brachial PWV (11.2 ± 2.4 m/s to 11.1 ± 2.2 m/s, Δ -0.2 ± 2.5 m/s, p = 0.72). The carotid artery was dilated more in control participants than hypertensive Veterans (Δ 0.54 ± 0.19 mm vs. 0.42 ± 0.12 mm, p = 0.022). Brachial artery dilation was similar between the two groups (Δ 0.55 ± 0.26 mm vs. 0.51 ± 0.20 mm, p = 0.46). In older Veterans without known cardiovascular disease, NTG-induced vasodilation increased elastic artery stiffness but did not change muscular artery stiffness. Increased central arterial stiffness and a decrease in the arterial stiffness gradient could offset some of the benefits of lowering blood pressure in older patients who are prescribed vasodilators as an antihypertensive therapy. Elastic artery stiffening with vasodilation warrants further investigation, as it may be important for antihypertensive medication selection and influence CVD development.

Keywords: Extracellular matrix; Hypertension; Smooth muscle; Vascular stiffness; Vasodilation.

Figure 1:

Diagram of the timeline for baseline and post-administration of 400 mcg sublingual nitroglycerin (NTG). After NTG administration, participants were monitored for at least 10 minutes or until blood pressure and heart rate returned to baseline. BP – Blood pressure, PWA – pulse wave analysis, cfPWV – carotid-femoral pulse wave velocity, CCA US – common carotid artery ultrasound, BA US – brachial artery ultrasound.

Figure 2:

Graphical representation of the methods used to control for the blood pressure dependence of carotid artery stiffness for a representative participant. Baseline data are shown as black circles and NTG data is shown as gray squares. For conventional stiffness calculations NTG decreased Peterson’s elastic modulus (PEM) (318 to 296 mmHg) but blood pressure also decreased. NTG increased PEM (329 to 369 mmHg) after adjusting stiffness calculation at a constant 120/80mmHg blood pressure.

Figure 3:

Despite causing approximately 10mmHg decreases in mean arterial pressure (MAP), nitroglycerin (NTG) administration A. increased carotid artery Petersons’ elastic modulus (PEM), B. did not change brachial artery PEM, and C. increased carotid-femoral pulse wave velocity (cfPWV). Abbreviations: CT – Control, HT – hypertensive

Figure 4:

A. Carotid artery passive stiffness from modeling was elevated in hypertensive participants while carotid artery active stiffness, brachial artery passive stiffness, and brachial artery active stiffness were not different between groups. B. Carotid artery basal smooth muscle tone was lower in hypertensive participants and brachial artery basal smooth muscle tone was similar between groups. C. For the carotid artery, a similar percentage of baseline SBP was supported by active and passive elements of the artery wall. For the brachial artery, the majority of baseline SBP was supported by active components of the artery wall for both groups.

Figure 5:

Proposed mechanism for elastic artery stiffening with vasodilation in older adults. With vasodilation, decreasing smooth muscle tone, vascular smooth muscle supports less mechanical load and the ECM supports more mechanical load. If the ECM is stiffer than the smooth muscle (as is likely the case in older adults), vasodilation shifting load from smooth muscle to the ECM will make the artery stiffer. Figure created with images from Servier Medical Art.