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Hemopexin activity is associated with angiotensin II responsiveness in humans

Krikken, Jan A.a; Lely, Anna T.a; Bakker, Stephan J.L.a; Borghuis, Theob; Faas, Marijke M.b; van Goor, Harryb; Navis, Gerjana; Bakker, Winston W.b

doi: 10.1097/HJH.0b013e32835c1727
ORIGINAL PAPERS: Pathophysiological aspects

Background: Hemopexin, an acute phase protein, can downregulate the angiotensin (ang) II type 1 receptor (AT1-R) in vitro. Whether hemopexin is involved in the responsiveness to ang II in vivo is unknown. Therefore, we tested whether variations in endogenous hemopexin activity are associated with the responsiveness of blood pressure to ang II in healthy volunteers.

Method: Healthy men (n = 33, age 26 ± 9) were studied in balance on low sodium (50 mmol Na+ per 24 h) and high sodium (200 mmol Na+ per 24 h) diet, respectively. After baseline measurements of blood pressure, ang II was infused at 0.3, 1 and 3 ng/kg per min for 1 h per dose. Hemopexin activity was measured at baseline in EDTA–plasma samples by an amidolytic assay with a chromogenic substrate suitable for hemopexin activity evaluation.

Results: During high sodium the hemopexin activity was lower; 1.6 × 105 (0.6 × 105 − 4.7 × 105) versus 2.8 × 105 (1.1 × 105 − 5.1 × 105) arbitrary units (P < 0.01) and the pressor response to 3 ng ang II/kg per minute larger than during low sodium (17.6 ± 6.5 versus 14.6 ± 6.9 mmHg, P < 0.01). Hemopexin activity negatively correlated with the pressor response to ang II during either type of sodium intake (high sodium: r = 0.42, P < 0.05; low sodium: r = 0.35, P < 0.05).

Conclusion: These in-vivo data obtained in healthy individuals support recent in-vitro data showing that active hemopexin downregulates the availability of the AT1-R. Therefore, activated hemopexin might be considered as a factor mediating ang II effects upon blood pressure by modulating AT1-R availability.

aDivision of Nephrology, Department of Internal Medicine

bDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence to Winston W. Bakker, Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.Tel: +31 50 361 9527; fax: +31 50 361 9107; e-mail: w.w.bakker@umcg.nl

Abbreviations: ang II, angiotensin II; APRC, active plasma renin concentration; AT1-R, angiotensin II type I receptor; MAP, mean arterial pressure; S2302, H-D-Pro-Phe-Arg-pNA.2HCl

Received 9 February, 2012

Revised 12 July, 2012

Accepted 30 October, 2012

© 2013 Lippincott Williams & Wilkins, Inc.