TITLE:
Can Sitaglipten Attenuate Hypertension, Myocardial Changes and Vascular Reactivity Induced by Long Term Blockade of Nitric Oxide Synthesis in the Rat?
AUTHORS:
Mervat E. Mohamed
KEYWORDS:
Glucagon-Like Peptide-1, Glucagon-Like Peptide-1 Receptor, Incretin, Diabetes, Blood Pressure, Heart Failure, Vasodilatation, Sympathetic Activation, Blood Pressure, L-Name, Sitaglipten, Renin Angiotensin System, Captopril
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.4 No.7,
July
18,
2014
ABSTRACT: Background: Glucagon-like peptide-1 (GLP-1)
is an incretin hormone with insulinotropic properties that regulates glucose metabolism.
GLP-1 receptors are the most extensively key modulators of lipid and glucose
homeostasis. They are predominantly expressed in adipose tissues, some non
adipose tissues including heart, kidney, spleen, and all relevant cells of the
vasculature: endothelial cells, smooth muscle cells, and macrophages. The
vascular distribution suggests their involvement in the control of cardiovascular
function. Objective: The present experiment was designed to study the effect of
sitaglipten alone or in combination with captopril on blood pressure,
antioxidant enzymes, vascular reactivity and cardiac hypertrophy in NG-nitro-L-arginine
methylester (L-NAME) induced hypertension in rats. Methods: One hundred male
albino rats weighing from 150 - 200 g were included in this study. Rats were
divided into two main groups. Group I, (20 rats) served as a control group for
group II, and received 1 ml of physiological saline (0.9%), orally for seven
weeks. Group II: hypertensive group, (80 rats) was given daily L-NAME in a dose
of 40 mg/kg orally for seven weeks. Rats were further subdivided into A, B, C,
and D, each of 20 rats. Group-A, received 1 ml of distilled water daily orally
for six weeks, starting one week after L-NAME administration. Groups B, C and D
were treated with daily sitaglipten (10 mg/kg b.wt. orally) and captopril (100 mg/kg
b.wt. orally), alone or together for six weeks. Blood pressure, serum tumor
necrosis factor-α (TNF-α), body weight (BW) and heart weight
(HW) were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) were
estimated in cardiac tissues. Thoracic aorta was isolated and the aortic rings
were allowed to achieve maximal tension by cumulative addition of phenylephrine
(PE) (10-9-10-5 M) to the bath solution. Results: Sitaglipten and captopril,
alone or together produced significant decreases in blood pressure and TNF-α. Higher oxidative stress accompanying
hypertension was significantly reduced by sitaglipten and captopril treatment.
The results showed that both drugs significantly attenuated the augmented
contractile response to PE in hypertensive rats. In addition, they inhibited
the cardiac hypertrophy (reduction in HW/BW ratio). Conclusion: These data
suggest that DPP4 inhibitor (sitaglipten) “is away from being insulinotropic
and regulates glucose metabolism”, contributes to normal regulation of blood
pressure and exerts protective effects in hypertension via many mechanisms, as
inhibition of generation of free radicals.