Conditions: Hypertension Diabetes Type 2
Keywords: DPPIV inhibitors ACE inhibitors Bradykinin glucagon-like peptide (GLP-1) BNP diabetes hypertension
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 44
Healthy volunteers: yes

Brief summary:
The investigators would like to find out if sitagliptin (dipeptidyl peptidase-4 or DPP4 inhibition), a drug to treat diabetes, affects blood vessel relaxation in healthy people receiving enalapril (angiotensin converting enzyme or ACE inhibition), a blood pressure medicine. Understanding how these drugs interact in healthy people will help us learn their potential effects in people who have diabetes.

Detailed description:
To test the hypothesis that DPPIV inhibition with sitagliptin potentiates the vasodilator response to substance P in the presence of ACE inhibition with enalaprilat and to BNP and GLP-1 even in the presence of ACE inhibition. The aim promises to provide important new data regarding the mechanism of action of DPPIV inhibitors and interactive effects of these two drug classes used in a growing population of diabetic patients.

Arms:
arm 1: The effect of vehicle and enalaprilat on the forearm blood flow and t-PA responses to bradykinin and substance P are studied after administration of placebo or sitagliptin (DPP4 inhibition). arm 2: The effect of vehicle and enalaprilat (ACE inhibition) on the forearm blood flow and t-PA responses to substance P and bradykinin are studied after administration of sitagliptin (DPP4 inhibition) or placebo arm 3: The effect of vehicle and enalaprilat (ACE inhibition) on the forearm blood flow and t-PA responses to glucagon-like peptide-1 and brain natriuretic pepdie are studied after administration of placebo or sitagliptin (DPP4 inhibition). arm 4: The effect of vehicle and enalaprilat on the forearm blood flow and t-PA responses to glucagon-like peptide and brain natriuretic peptide are studied after administration of placebo or sitagliptin (DPP4 inhibition).

Interventions: intervention 1: Sitagliptin (DPP4 inhibitor) intervention 2: Substance P, intervention 3: bradykinin intervention 4: enalaprilat (ACE inhibitor) intervention 5: Glucagon-like peptide 1 intervention 6: brain natriuretic peptide
Intervention descriptions: intervention 1: Sitagliptin 200 mg (DPP4 inhibitor) or matching placebo will be given one hour prior to intra-arterial infusions intervention 2: Substance P intra-brachial artery (2,4,8 pmol/min) intervention 3: bradykinin intra-brachial artery (23.6, 47.2, and 94.3 pmol/min) intervention 4: intra-brachial artery(0.33 µg/min per 100 mL forearm volume) intervention 5: intra-brachial artery (0.45-3.60 pmol/min) intervention 6: Intra-brachial artery (0.90, 1.80 and 3.6 pmol/min)

Protocol document: