Vascular and metabolic effects of the haem oxygenase-1 inducer haem arginate in subjects with the metabolic syndrome: A translational cross-over study. (January 2016)

• Record Type: Journal Article
• Authors: Dekker, Douwe; Dorresteijn, Mirrin J; Peters, Wilbert HM; Bilos, Albert; Pennings, Sebastiaan WC; Wagener, Frank ADTG; Smits, Paul
• Is Part Of: Diabetes & vascular disease research. Volume 13:Number 1(2016:Jan.)
• Page Start: 41
• Page End: 48
• Publication Date: 2016-01
• Subjects: Translational medical research -- haem arginate -- haem oxygenase -- metabolic syndrome -- insulin resistance -- endothelial function; Diabetic angiopathies -- Periodicals; 616.462005
• DOI: 10.1177/1479164115605047
• Languages: English
• ISSNs: 1479-1641

Abstract

This translational randomized and vehicle-controlled cross-over study was performed to assess the impact of haem arginate treatment on haem oxygenase-1 induction, endothelial function and insulin sensitivity in subjects with the metabolic syndrome ( n = 14). Both treatment periods consisted of 5 days. Haem arginate or vehicle (l -arginine) was administered intravenously on Days 1 and 3. Forearm blood flow in response to acetylcholine and nitroglycerine was measured by venous occlusion plethysmography (Day 3), insulin sensitivity by a hyperinsulinaemic clamp procedure (Day 5). Haem arginate did not improve endothelial function or insulin sensitivity but significantly reduced the vasodilator response to nitroglycerine ( p < 0.01). These negative findings are in contrast to the preclinical data, which may be due to short duration of therapy and limited haem oxygenase-1 induction as well as interference by markedly elevated plasma haem levels observed after haem arginate treatment ( p < 0.01). Future studies should pay attention to the delicate balance between sufficient dosing and timely normalization of plasma haem levels.