Sitagliptin significantly lowered mean arterial blood pressure in young prehypertensive spontaneously hypertensive rats compared to vehicle (104 vs 123 mmHg, P<0.01).
Does sitagliptin reduce blood pressure and improve renal function in spontaneously hypertensive rats?
DPPIV inhibition with sitagliptin attenuates the rise in blood pressure in young prehypertensive spontaneously hypertensive rats, likely via inhibition of renal NHE3 activity.
Absolute Event Rate: 104% vs 123%
p-value: p=<0.01
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 0.05). 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.
Pacheco et al. (Sat,) 在 Hypertension 上进行了一项研究。在平均动脉压方面对 Sitagliptin 与溶剂对照处理的 SHR 以及血压正常的 Wistar-Kyoto 大鼠进行了评估 (p=<0.01)。与溶剂对照相比，Sitagliptin 显著降低了年轻高血压前期自发性高血压大鼠的平均动脉压 (104 vs 123 mmHg, P<0.01)。