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J Hypertens. 2011 Mar;29(3):520-8. doi: 10.1097/HJH.0b013e328341939d.

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

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1
Heart Institute (InCor), Medical School, Brazil.

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.

PMID:
21150640
DOI:
10.1097/HJH.0b013e328341939d
[Indexed for MEDLINE]

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