Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats.

Abstract:

OBJECTIVES:The present study aimed to assess the effect of the specific dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin on blood pressure and renal function in young prehypertensive (5-week-old) and adult spontaneously hypertensive rats (SHRs; 14-week-old). METHODS:Sitagliptin (40 mg/kg twice daily) was given by oral gavage to young (Y-SHR + IDPPIV) and adult (A-SHR + IDPPIV) SHRs for 8 days. Kidney function was assessed daily and compared with age-matched vehicle-treated SHR (Y-SHR and A-SHR) and with normotensive Wistar-Kyoto rats (Y-WKY and A-WKY). Arterial blood pressure was measured in these animals at the end of the experimental protocol. Additionally, Na/H exchanger isoform 3 (NHE3) function and expression in microvilli membrane vesicles were assessed in young animals. RESULTS:Mean arterial blood pressure of Y-SHR + IDPPIV was significantly lower than that of Y-SHR (104 ± 3 vs. 123 ± 5 mmHg, P < 0.01) and was similar to Y-WKY (94 ± 4 mmHg, P > 0.05). Compared to Y-SHR, Y-SHR + IDPPIV exhibited enhanced cumulative urinary flow and sodium excretion and decreased NHE3 activity and expression in proximal tubule microvilli. In the A-SHR, sitagliptin treatment had no significant effect on either renal function or arterial blood pressure. CONCLUSION:Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Pacheco BP,Crajoinas RO,Couto GK,Davel AP,Lessa LM,Rossoni LV,Girardi AC

doi

10.1097/HJH.0b013e328341939d

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

520-8

issue

3

eissn

0263-6352

issn

1473-5598

journal_volume

29

pub_type

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