Endothelial Function, Obese
Conditions
Brief summary
To evaluate the efficacy of arginase inhibition on endothelial function in humans with obesity.
Detailed description
The study is performed on one group of subjects with body mass index \>35 and the absence of type 2 diabetes. Inclusion criteria: Body mass index \>35 kg/m2. Exclusion criteria: Age \>80 years. Type 2 diabetes defined as \>7 mmol/L in fasting plasma glucose or \>11 mmol/L following 2h of oral glycemic load. Myocardial infarction/unstable angina within 6 weeks prior to the study. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants), Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm. Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol. Participant in an ongoing study. Unwillingness to participate following oral and written information. Forearm blood flow is determined by venous occlusion plethysmography. Endothelium-dependent vasodilatation is determined during intra-brachial artery infusion of serotonin (21, 70 and 210 ng/min). Endothelium-independent vasodilatation is determined by infusion of sodium nitroprusside (SNP; 1, 3 and 10 µg/min). Each dose is given for 2 min at a rate of 2.5 ml/min. Data are expressed as percentage change in forearm blood from baseline flow. Fifteen subjects are included. On the day of the study the subject arrives to the laboratory after having a light breakfast. Forearm vessels of the non-dominant arm are cannulated and forearm blood flow is determined as described above. Baseline endothelium-dependent and endothelium-independent vasodilatation is determined by intra-arterial infusions of serotonin and SNP, respectively. Thereafter an intra-arterial infusion of the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) is administered as an intra-arterial infusion at a rate of 0.1 mg/min and is maintained for 120 min. The dose is based on a previous study by our group demonstrating improved endothelial function. Endothelium-dependent and -independent vasodilatation is reassessed at 120 min of infusion.
Interventions
Sponsors
Karolinska Institutet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
BMI \>35kg/m2
Exclusion criteria
Age \>80 years. Type 2 diabetes defined as \>7 mmol/L in fasting plasma glucose or \>11 mmol/L following 2h of oral glycemic load. Myocardial infarction/unstable angina within 6 weeks prior to the study. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants), Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm. Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol. Participant in an ongoing study. Unwillingness to participate following oral and written information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelium-dependent change in forearm blood flow | 120 min intraarterial infusion of the arginase inhibitor nor-NOHA | Percentage change in forearm blood flow from baseline induced by the endothelium-dependent vasodilator serotonin during arginase blockade vs. saline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelium-independent change in forearm blood flow | 120 min intraarterial infusion of the arginase inhibitor nor-NOHA | Percentage change in forearm blood flow from baseline induced by the endothelium-independent vasodilator nitroprusside during arginase blockade vs. saline. |
Countries
Sweden
Outcome results
None listed