Vascular and metabolic effects of the haem oxygenase-1 inducer haem arginate in subjects with the metabolic syndrome: A translational cross-over study.
Diab Vasc Dis Res
; 13(1): 41-8, 2016 Jan.
Article
in En
| MEDLINE
| ID: mdl-26468161
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arginine
/
Vasodilation
/
Insulin Resistance
/
RNA, Messenger
/
Endothelium, Vascular
/
Metabolic Syndrome
/
Heme Oxygenase-1
/
Heme
Type of study:
Clinical_trials
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Diab Vasc Dis Res
Journal subject:
ANGIOLOGIA
/
ENDOCRINOLOGIA
Year:
2016
Type:
Article
Affiliation country:
Netherlands