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Acute reductions in haematocrit increase flow‐mediated dilatation independent of resting nitric oxide bioavailability in humans
Author(s) -
Hoiland Ryan L.,
Tremblay Joshua C.,
Stacey Benjamin S.,
Coombs Geoff B.,
NowakFlück Daniela,
Tymko Michael M.,
Patrician Alexander,
Stembridge Mike,
Howe Connor A.,
Bailey Damian M.,
Green Daniel J.,
MacLeod David B.,
Ainslie Philip N.
Publication year - 2020
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp280141
Subject(s) - nitric oxide , vasodilation , brachial artery , medicine , vasoconstriction , blood flow , chemistry , anesthesia , endocrinology , blood pressure
Key points Changes in haematocrit influence nitric oxide signalling through alterations in shear stress stimuli and haemoglobin scavenging of nitric oxide; these two regulatory factors have not been assessed simultaneously Isovolumic haemodilution led to a marked increase in brachial artery flow‐mediated dilatation in humans The increase in flow‐mediated dilatation occurred in the face of an unaltered shear stress stimulus for vasodilatation and reduced resting steady‐state nitric oxide levels in the blood Collectively, our data point towards haemoglobin scavenging of nitric oxide as a key regulatory factor of brachial flow‐mediated dilatation and highlight the importance of the simultaneous consideration of nitric oxide production and inactivation when investigating vascular function in humansAbstract Haemoglobin (Hb) may impact the transduction of endothelium‐dependent and nitric oxide (NO)‐mediated vasodilator activity, given its contribution to shear stress stimuli and diverse biochemical reactions with NO. We hypothesized that an acute reduction in [Hb] and haematocrit (Hct) would increase brachial artery flow‐mediated dilatation (FMD). In 11 healthy males (28 ± 7 years; 23 ± 2 kg m −2 ), FMD (Duplex ultrasound), arterial blood gases, Hct and [Hb], blood viscosity, and NO metabolites (ozone‐based chemiluminescence) were measured before and after isovolumic haemodilution, where ∼20% of whole blood was removed and replaced with 5% human serum albumin. Haemodilution reduced Hct by 18 ± 2% ( P < 0.001) and whole blood viscosity by 22 ± 5% ( P < 0.001). Plasma nitrite ( P = 0.01), S ‐nitrosothiols ( P = 0.03) and total red blood cell NO ( P = 0.001) were collectively reduced by ∼15–40%. Brachial artery FMD increased by ∼160% from 3.8 ± 2.1 to 9.7 ± 4.5% ( P = 0.004). Statistical covariation for the shear stress stimulus did not alter FMD, indicating that the increase in FMD was not directly related to alterations in whole blood viscosity and the shear stimulus. Collectively, these findings indicate that haemoglobin scavenging of NO appears to be an important factor in the regulation of FMD under normal conditions through constraint of endothelium‐dependent NO‐mediated vasodilatation in healthy humans.