Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats
| Autor: | Yoshihide Fujisawa, Hiroyuki Kobori, Abu Sufiun, Akira Nishiyama, Tsutomu Masaki, Asadur Rahman, Hirohito Mori, Koji Ohmori, Kazi Rafiq, Masakazu Kohno, Daisuke Nakano |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Mean arterial pressure Pyrrolidines Physiology Dipeptidyl Peptidase 4 Adamantane Blood Pressure Pharmacology dipeptidyl peptidase-4 (DPP-4) inhibitors Urine sodium Article dipping pattern Excretion Glucagon-Like Peptide 1 Heart Rate Internal medicine Heart rate Nitriles Internal Medicine medicine Animals Telemetry Vildagliptin Arterial Pressure Circadian rhythm Sodium Chloride Dietary Dipeptidyl peptidase-4 Antihypertensive Agents Dahl salt-sensitive rats Injections Intraventricular Dipeptidyl-Peptidase IV Inhibitors Rats Inbred Dahl Dose-Response Relationship Drug business.industry Sodium Circadian Rhythm Rats Blood pressure Endocrinology Hypertension Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Hypertension research : official journal of the Japanese Society of Hypertension. 38(4) |
| ISSN: | 1348-4214 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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