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Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats.
- Source :
-
Hypertension research : official journal of the Japanese Society of Hypertension [Hypertens Res] 2015 Apr; Vol. 38 (4), pp. 237-43. Date of Electronic Publication: 2015 Jan 15. - Publication Year :
- 2015
-
Abstract
- A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors have antihypertensive effects. Here, we aim to examine the effect of vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian-dipping pattern during the development of salt-dependent hypertension in Dahl salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl) plus vehicle or vildagliptin (3 or 10 mg kg(-1) twice daily by oral gavage) for 7 days. Blood pressure was measured by the telemetry system. High-salt diet for 7 days significantly increased the mean arterial pressure (MAP), systolic blood pressure (SBP) and were also associated with an extreme dipping pattern of blood pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels and attenuated the development of salt-induced hypertension. Furthermore, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern of blood pressure. In contrast, intracerebroventricular infusion of vildagliptin (50, 500 or 2500 μg) did not alter MAP and heart rate in DSS rats. These data suggest that salt-dependent hypertension initially develops with an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may elicit beneficial antihypertensive effects, including the improvement of abnormal circadian blood pressure pattern, by enhancing urinary sodium excretion.
- Subjects :
- Adamantane administration & dosage
Adamantane therapeutic use
Animals
Arterial Pressure drug effects
Dipeptidyl Peptidase 4 metabolism
Dipeptidyl-Peptidase IV Inhibitors administration & dosage
Dose-Response Relationship, Drug
Glucagon-Like Peptide 1 metabolism
Heart Rate drug effects
Injections, Intraventricular
Male
Nitriles administration & dosage
Pyrrolidines administration & dosage
Rats
Rats, Inbred Dahl
Sodium urine
Sodium Chloride, Dietary adverse effects
Telemetry
Vildagliptin
Adamantane analogs & derivatives
Antihypertensive Agents therapeutic use
Blood Pressure drug effects
Circadian Rhythm drug effects
Dipeptidyl-Peptidase IV Inhibitors therapeutic use
Hypertension drug therapy
Hypertension physiopathology
Nitriles therapeutic use
Pyrrolidines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1348-4214
- Volume :
- 38
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Hypertension research : official journal of the Japanese Society of Hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 25588850
- Full Text :
- https://doi.org/10.1038/hr.2014.173