Nitric oxide is fundamental to neurovascular coupling in humans

被引:63
作者
Hoiland, Ryan L. [1 ,2 ]
Caldwell, Hannah G. [1 ]
Howe, Connor A. [1 ]
Nowak-Fluck, Daniela [1 ]
Stacey, Benjamin S. [3 ]
Bailey, Damian M. [3 ]
Paton, Julian F. R. [4 ]
Green, Daniel J. [5 ]
Sekhon, Mypinder S. [6 ]
Macleod, David B. [7 ]
Ainslie, Philip N. [1 ]
机构
[1] Univ British Columbia Okanagan, Sch Hlth & Exercise Sci, Ctr Heart Lung & Vasc Hlth, Kelowna, BC V1V 1V7, Canada
[2] Vancouver Gen Hosp, Dept Anesthesiol Pharmacol & Therapeut, 899 West 12th Ave, Vancouver, BC V5Z 1M9, Canada
[3] Univ South Wales, Fac Life Sci & Educ, Neurovasc Res Lab, Pontypridd CF37 4BB, M Glam, Wales
[4] Univ Auckland, Fac Med & Hlth Sci, Dept Physiol, Pk Rd, Auckland 1142, New Zealand
[5] Univ Western Australia, Sch Human Sci Exercise & Sport Sci, Nedlands, WA 6009, Australia
[6] Univ British Columbia, Vancouver Gen Hosp, Dept Med, Div Crit Care Med, West 12th Ave, Vancouver, BC V5Z 1M9, Canada
[7] Duke Univ, Dept Anesthesiol, Human Pharmacol & Physiol Lab, Med Ctr, Durham, NC 27708 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2020年 / 598卷 / 21期
关键词
cerebral blood flow; cerebral metabolism; humans; neurovascular coupling; nitric oxide; CEREBRAL-BLOOD-FLOW; TRANSCRANIAL DOPPLER ULTRASOUND; INHIBITOR L-NMMA; SYNTHASE INHIBITOR; VIBRISSAL STIMULATION; CAPILLARY PERICYTES; S-NITROSOHEMOGLOBIN; NEURONAL-ACTIVITY; VASODILATION; HYPEREMIA;
D O I
10.1113/JP280162
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Key points Preclinical models have demonstrated that nitric oxide is a key component of neurovascular coupling; this has yet to be translated to humans. We conducted two separate protocols utilizing intravenous infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric oxide on neurovascular coupling in humans. Isovolumic haemodilution did not alter neurovascular coupling. Intravenous infusion of a nitric oxide synthase inhibitor reduced the neurovascular coupling response by similar to 30%, indicating that nitric oxide is integral to neurovascular coupling in humans. Nitric oxide is a vital neurovascular signalling molecule in preclinical models, yet the mechanisms underlying neurovascular coupling (NVC) in humans have yet to be elucidated. To investigate the contribution of nitric oxide to NVC in humans, we utilized a visual stimulus paradigm to elicit an NVC response in the posterior cerebral circulation. Two distinct mechanistic interventions were conducted on young healthy males: (1) NVC was assessed during intravenous infusion of saline (placebo) and the non-selective competitive nitric oxide synthase inhibitorN(G)-monomethyl-l-arginine (l-NMMA, 5 mg kg(-1)bolus & subsequent 50 mu g kg(-1) min(-1)maintenance dose;n = 10). The order of infusion was randomized, counterbalanced and single blinded. A subset of participants in this study (n = 4) underwent a separate intervention with phenylephrine infusion to independently consider the influence of blood pressure changes on NVC (0.1-0.6 mu g kg(-1) min(-1)constant infusion). (2) NVC was assessed prior to and following isovolumic haemodilution, whereby 20% of whole blood was removed and replaced with 5% human serum albumin to reduce haemoglobin concentration (n = 8). For both protocols, arterial and internal jugular venous blood samples were collected at rest and coupled with volumetric measures of cerebral blood flow (duplex ultrasound) to quantify resting cerebral metabolic parameters.l-NMMA elicited a 30% reduction in the peak (P = 0.01), but not average (P = 0.11), NVC response. Neither phenylephrine nor haemodilution influenced NVC. Nitric oxide signalling is integral to NVC in humans, providing a new direction for research into pharmacological treatment of humans with dementia.
引用
收藏
页码:4927 / 4939
页数:13
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