title: Acute hemodynamic and renal effects of glucagon-like peptide 1 analog and dipeptidyl peptidase-4 inhibitor in rats.
abstract: BACKGROUND
  Glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase-4 (DPP4) inhibitors are a newer class of antidiabetics named as incretin-based therapy. In addition to the homeostatic control of glucose, the incretin-based therapy has shown beneficial effects on the cardiovascular system in preclinical and clinical studies. However, there is limited information on their renal effects. To this end, we assessed the acute hemodynamic and renal effects of a GLP-1 analog, Liraglutide, and a DPP4 inhibitor, MK-0626.
  
  
  METHODS
  Experiments were performed in anesthetized male Sprague-Dawley rats. Three ascending doses of Liraglutide (3, 9, and 27 nmol/kg/h) or MK-0626 (1 mg/kg) with or without GLP-1 peptide (2.4, 4.8, or 9.6 pmol/kg/min) were administered. Blood pressure (BP) and heart rate (HR) were recorded from an indwelling catheter. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by inulin and para-aminohippurate clearance, respectively. Renal excretory function was assessed in metabolic studies.
  
  
  RESULTS
  Both Liraglutide and MK-0626 plus GLP-1 evoked significant diuretic and natriuretic responses and increased GFR. MK-0626 alone increased RBF. Liraglutide at 27 nmol//kg/h and MK-0626 plus GLP-1 at 9.6 pmol/kg/min also increased HR, whereas BP was not affected.
  
  
  CONCLUSIONS
  The results of the present study demonstrated that a GLP-1 analog and a DPP4 inhibitor may have beneficial effects on renal sodium and water handling. Additionally, the DPP4 inhibitor, MK-0626, favorably affects renal hemodynamics by increasing RBF. However, exceedingly high levels of GLP-1 receptor agonists may adversely affect the cardiovascular system in acute setting, as demonstrated by an acute increase in HR.
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. xiaoyan_zhou@merck.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. chin-hu.huang@merck.com.
authors.forename: Chin-hu
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. zhege_lao@merck.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Lao
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. apocai1@its.jnj.com.|Janssen Research and Development, Cardiovascular and Metabolic Disease, 1516 Welsh and McKean Roads, Spring House, PA, 19477, USA. apocai1@its.jnj.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pocai
authors.affiliation: In Vivo Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. gail_forrest@merck.com.
authors.forename: Gail
authors.initials: G
authors.lastname: Forrest
authors.affiliation: In Vivo Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. olga_urosevic@merck.com.
authors.forename: Olga
authors.initials: O
authors.lastname: Price
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. Sophie_Roy@me.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. david_kelley@merck.com.
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
authors.affiliation: Department of Cardiometabolic Diseases, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. kasullivan955@gmail.com.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sullivan
authors.affiliation: In Vivo Pharmacology, Merck Research Laboratories, 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA. runforrest@comcast.net.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Forrest
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D054795:Incretins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D000069450:Liraglutide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; C570834:MK0626; D014230:Triazoles; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1