Sodium Nitroglycerin and Hypercapnic Stimuli Reduce Cerebral Vascular Bed Compliance in Humans

Abstract

Human cerebral arteries dilate to various stimuli and this change in contractile state is often quantified as a steady-state change in vascular resistance. In oscillatory blood flow, compliance of the vascular bed also contributes to the regulation of cerebral perfusion. However, very little is known about the impact of cerebral dilation on cerebral vascular bed compliance. Therefore, the present study examined the impact of cerebral vasodilatory stimuli on cerebrovascular compliance in humans. Fifteen young, healthy adults (27 ± 5 years, 7 females) participated in the present study. Participants completed a sodium nitroglycerin (SNG) protocol involving a 2-minute baseline period, administration of one 0.4 mg sublingual spray of SNG, followed by 10 minutes of data collection. Following the completion of the SNG protocol, participants rested for at least 5 minutes after which the hypercapnia protocol was completed. Following a 2-minute baseline period, participants breathed a low percentage (5-6%) carbon dioxide (CO2)gas mixture for 4 minutes followed by a 3-minute recovery period breathing room air. Throughout the experimental protocols, blood pressure (BP) waveforms (finger photoplethysmography; Finapres Medical Systems) and middle cerebral artery blood velocity (BV) waveforms (transcranial Doppler ultrasound; Multigon Industries) were collected in the supine position. Five individual BP and corresponding BV waveforms were extracted during each protocol's baseline period, at each minute of SNG and CO2, and during the last minute of the CO2 recovery period. The waveforms were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci was 5.0e-4 ± 2.3e-4 cm·s-1·mmHg-1 at baseline and decreased significantly by minute 7 of SNG administration (P = 0.01, d = 1.07). Overall, Ci decreased by 29% to its nadir, 3.6e-4 ± 1.2e-4 cm·s-1·mmHg-1, at minute 10 of the protocol (P = 0.01, d = 0.98). During the hypercapniaprotocol, Ci was 4.4e-4 ± 2.0e-4 cm·s-1·mmHg-1 at baseline and decreased significantly by minute 1 of breathing CO2 (P = 0.003, d = 1.04). Overall, Ci was reduced by 30% to its lowest value of 3.1e-4 ± 1.4e-4 cm·s-1·mmHg-1 by minute 4 of hypercapnia (P < 0.001, d = 1.56). However, following 3 minutes of recovery, Ci increased to 4.2e-4 ± 1.5e-4 cm·s-1·mmHg-1, which was not different from baseline values (P = 0.86). BP remained unchanged during the SNG protocol (BSL: 87 ± 8 mmHg, Min 10: 89 ± 8 mmHg; P = 0.99), while it increased by 5 mmHg during the hypercapnia protocol (BSL: 86 ± 10 mmHg, Min 4: 91 ± 10 mmHg; P < 0.001, d = 1.44). However, no significant relationship was observed between the change in BP and the change in Ci with hypercapnia (r = -0.09, P = 0.75). Both vasodilatory stimuli reduced Ci by approximately 30% from supine baseline values. The attenuation of Ci likely relates to the predominance of collagen fibers in supporting wall tension during vessel distension.