1.
Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans.
Marney, A, Kunchakarra, S, Byrne, L, Brown, NJ
Hypertension (Dallas, Tex. : 1979). 2010;(4):728-33
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Abstract
Dipeptidyl peptidase-IV inhibitors improve glucose homeostasis in type 2 diabetics by inhibiting degradation of the incretin hormones. Dipeptidyl peptidase-IV inhibition also prevents the breakdown of the vasoconstrictor neuropeptide Y and, when angiotensin-converting enzyme (ACE) is inhibited, substance P. This study tested the hypothesis that dipeptidyl peptidase-IV inhibition would enhance the blood pressure response to acute ACE inhibition. Subjects with the metabolic syndrome were treated with 0 mg of enalapril (n=9), 5 mg of enalapril (n=8), or 10 mg enalapril (n=7) after treatment with sitagliptin (100 mg/day for 5 days and matching placebo for 5 days) in a randomized, cross-over fashion. Sitagliptin decreased serum dipeptidyl peptidase-IV activity (13.08±1.45 versus 30.28±1.76 nmol/mL/min during placebo; P≤0.001) and fasting blood glucose. Enalapril decreased ACE activity in a dose-dependent manner (P<0.001). Sitagliptin lowered blood pressure during enalapril (0 mg; P=0.02) and augmented the hypotensive response to 5 mg of enalapril (P=0.05). In contrast, sitagliptin attenuated the hypotensive response to 10 mg of enalapril (P=0.02). During sitagliptin, but not during placebo, 10 mg of enalapril significantly increased heart rate and plasma norepinephrine concentrations. There was no effect of 0 or 5 mg of enalapril on heart rate or norepinephrine after treatment with either sitagliptin or placebo. Sitagliptin enhanced the dose-dependent effect of enalapril on renal blood flow. In summary, sitagliptin lowers blood pressure during placebo or submaximal ACE inhibition; sitagliptin activates the sympathetic nervous system to diminish hypotension when ACE is maximally inhibited. This study provides the first evidence for an interactive hemodynamic effect of dipeptidyl peptidase-IV and ACE inhibition in humans.
2.
[The efficiency of combinations of Enalapril and long-acting Nifedipin and Moxonidine in patients with arterial hypertension and a metabolic syndrome].
Mananko, EI, Vorob'eva, EV, Kalashnikova, TP, Bushkova, EA, Krasnova, NM, Idrisova, EM, Vengerovskiĭ, AI, Karpov, RS, Gruzdeva, OV, Kremenko, SV
Klinicheskaia meditsina. 2008;(7):56-61
Abstract
The aim of the study was to obtain a comparative evaluation of antihypertensive efficacy, tolerability and influence of combine therapy on myocardium mass, diastolic function of a left ventricle, lipid and carbohydrate exchange in patients with arterial hypertension in metabolic syndrome. Out of 40 examined cases 20 patients took enalapril and long-acting nifedipin and 20 ones--enalapril and moxonidine. All examination were been performed before administration of drugs and 6 months after the therapy. The dynamics of indices of ambulatory blood pressure monitoring, echocardiography, cycle ergometry, anthropometry, lipid, carbohydrate exchange and tolerability of conducted therapy was been evaluated. The use of this combination of the drugs may be recommended to be included in the treatment of arterial hypertension within the bounds of metabolic syndrome, as in most of cases they promote an achievement of target blood pressure level, have a cardioprotective action, high tolerability and favorable metabolic profile. The combination of enalapril and long-acting nifedipin has a more evident antihypertensive activity but a therapy with enalapril and moxonidine has a positive effect on the indices of carbohydrate exchange.