title: Dipeptidyl peptidase IV inhibition attenuates blood pressure rising in young spontaneously hypertensive rats.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Our data suggest that DPPIV inhibition attenuates blood pressure rising in young prehypertensive SHRs, partially by inhibiting NHE3 activity in renal proximal tubule.
authors.affiliation: Heart Institute (InCor), Medical School, Brazil.
authors.forename: Bruna Pm
authors.initials: BP
authors.lastname: Pacheco
authors.forename: Renato O
authors.initials: RO
authors.lastname: Crajoinas
authors.forename: Gisele K
authors.initials: GK
authors.lastname: Couto
authors.forename: Ana Paula C
authors.initials: AP
authors.lastname: Davel
authors.forename: Lucília M
authors.initials: LM
authors.lastname: Lessa
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Adriana Cc
authors.initials: AC
authors.lastname: Girardi
mesh_terms: D000375:Aging; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000068900:Sitagliptin Phosphate; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D014230:Triazoles; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate