Vascular Effects of Apelin In Vivo in Man
Alan G. Japp, MRCP*,*,
Nicholas L. Cruden, PhD*,
David A.B. Amer*,
Vivienne K.Y. Li, BSc*,
Ewan B. Goudie, BSc*,
Neil R. Johnston, MSc*,
Sushma Sharma, PhD ,
Ilene Neilson, BSc,
David J. Webb, MD, FRCP*,
Ian L. Megson, PhD,
Andrew D. Flapan, MD, MRCP and
David E. Newby, PhD, FRCP*
* Centre for Cardiovascular Science, University of Edinburgh, Chancellor's Building, Edinburgh, United Kingdom
Department of Diabetes, UHI Millennium Institute, Inverness, United Kingdom
Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom
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Figure 1 Study Design
Protocol 1: Dorsal hand vein infusions of (Pyr1)apelin-13 or apelin-36 (blue; nmol/min), sodium nitroprusside (SNP) (red; nmol/min) and saline, with coinfusion of norepinephrine. Protocol 2 (A and B): Intrabrachial infusions of (Pyr1)apelin-13 or apelin-36 (blue; nmol/min) and saline with venous blood sampling ( ). Protocol 3: Intrabrachial infusions of (Pyr1)apelin-13 (blue; nmol/min) and acetylcholine (yellow; µg/min) with coadministration of aspirin or placebo, and "nitric oxide clamp" or saline placebo. L-NMMA = L-N
G-monomethylarginine.
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Figure 2 DHV Diameter During Coinfusion of Norepinephrine
DHV diameter during coinfusion of norepinephrine and (A) incremental doses of (Pyr1)apelin-13 (solid squares) and single dose of SNP (solid diamonds; 0.6 nmol/min) and (B) incremental doses of apelin-36 (open squares) and single dose of SNP (open diamonds; 0.6 nmol/min). ***p < 0.001, paired Student t test. DHV = dorsal hand vein; other abbreviations as in Figure 1.
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Figure 3 Infused FBF
Infused FBF (A) in protocol 2A during infusion of (Pyr1)apelin-13 (top, solid squares; 1-way ANOVA) and apelin-36 (bottom, open squares; 1-way ANOVA) and (B) during incremental infusion of (Pyr1)apelin-13 (solid squares) versus apelin-36 (open squares); 2-way ANOVA with repeated measures. *p < 0.05, **p < 0.01, ***p < 0.001, post-hoc Bonferroni tests. ANOVA = analysis of variance; FBF = forearm blood flow.
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Figure 4 Infused FBF
Infused FBF (A) in protocol 2B during infusion of (Pyr1)apelin-13 (top, solid squares; 1-way ANOVA) and apelin-36 (bottom, open squares; 1-way ANOVA) and during incremental infusion of (Pyr1)apelin-13 (B) and apelin-36 (C) in the presence (solid squares) and absence (open squares) of saline washouts (for both: p > 0.05, 2-way ANOVA with repeated measures). **p < 0.01, ***p < 0.001, post-hoc Bonferroni tests. Abbreviations as in Figure 3.
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Figure 5 Plasma Apelin Concentration
Plasma apelin concentration in venous blood samples from infused (solid bars) and noninfused arm (open bars) during intrabrachial apelin-36 infusion. **p < 0.01, ***p < 0.001, 1-way ANOVA with post-hoc Bonferroni tests. Abbreviation as in Figure 3.
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Figure 6 Infused FBF in Subjects During Infusion
Infused FBF in subjects during infusion of (top row) (Pyr1)apelin-13 in the presence (solid squares) or absence (open squares) of nitric oxide (NO) clamp (left) or aspirin (right) and (bottom row) acetylcholine in the presence (solid circles) or absence (open circles) of NO clamp (left) or aspirin (right). p < 0.0001; 1-way ANOVA for dose responses to (Pyr1)apelin-13 and acetylcholine alone. For placebo versus NO clamp (AUC): (Pyr1)apelin-13, p < 0.01; acetylcholine, p < 0.05. For placebo versus aspirin (AUC): (Pyr1)apelin-13, p = 0.7; acetylcholine, p = 0.9. AUC = area under the curve; other abbreviations as in Figure 3.
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