BACKGROUND/AIMS: Abnormal baroreceptor reflex sensitivity (BRS) and elevated plasma neuropeptide Y (NPY) are prevalent in diabetic patients. The present study was conducted to determine whether NPY Y1 receptor (Y1R) and NPY Y2 receptor (Y2R) contribute to the regulatin of BRS in diabetic rats. METHODS: Diabetes mellitus (DM) rats with hyperlipidemia were developed by an emulsion diet enriched with fat, sucrose and fructose followed by streptozocin (STZ). Y1R and Y2R specific antagonists (BIBP 3226 and BIIE 0246) were administered by a mini-osmotic pump. Systolic blood pressure (SBP), heart rate (HR), BRS and heart functions, as well as the plasma NPY and lipid level were measured after treatment for 4 weeks. RESULTS: Both BIBP 3226 and BIIE 0246 treatment reversed the elevated total cholesterol (TC) and low density lipoprotein (LDL-C) level, and reduced high density lipoprotein (HDL-C) level in DM rats. BIIE 0246 may attenuate the increased triglyceride (TG) level in DM rats. In addition, neither BIBP 3226 nor BIIE 0246 treatment produced significant effects on BRS, SBP or HR (P>0.05) in DM rats, even after PE and SNP challenge. However, BIBP 3226 and BIIE 0246 further impaired LVSP, LVEDP, +dp/dtmax and -dp/dtmax. CONCLUSION: This study provided us with the evidence that the inhibition of peripheral Y1R and Y2R did not affect impaired BRS but amplified the deterioration of the compromised cardiac function in STZ-induced DM rats with hyperlipidemia.
BACKGROUND/AIMS: Abnormal baroreceptor reflex sensitivity (BRS) and elevated plasma neuropeptide Y (NPY) are prevalent in diabeticpatients. The present study was conducted to determine whether NPY Y1 receptor (Y1R) and NPY Y2 receptor (Y2R) contribute to the regulatin of BRS in diabeticrats. METHODS:Diabetes mellitus (DM) rats with hyperlipidemia were developed by an emulsion diet enriched with fat, sucrose and fructose followed by streptozocin (STZ). Y1R and Y2R specific antagonists (BIBP 3226 and BIIE 0246) were administered by a mini-osmotic pump. Systolic blood pressure (SBP), heart rate (HR), BRS and heart functions, as well as the plasma NPY and lipid level were measured after treatment for 4 weeks. RESULTS: Both BIBP 3226 and BIIE 0246 treatment reversed the elevated total cholesterol (TC) and low density lipoprotein (LDL-C) level, and reduced high density lipoprotein (HDL-C) level in DMrats. BIIE 0246 may attenuate the increased triglyceride (TG) level in DMrats. In addition, neither BIBP 3226 nor BIIE 0246 treatment produced significant effects on BRS, SBP or HR (P>0.05) in DMrats, even after PE and SNP challenge. However, BIBP 3226 and BIIE 0246 further impaired LVSP, LVEDP, +dp/dtmax and -dp/dtmax. CONCLUSION: This study provided us with the evidence that the inhibition of peripheral Y1R and Y2R did not affect impaired BRS but amplified the deterioration of the compromised cardiac function in STZ-induced DMrats with hyperlipidemia.
Authors: Liisa Ailanen; Laura H Vähätalo; Henriikka Salomäki-Myftari; Satu Mäkelä; Wendy Orpana; Suvi T Ruohonen; Eriika Savontaus Journal: Front Pharmacol Date: 2018-04-05 Impact factor: 5.810
Authors: Abigail C Lay; A Fern Barrington; Jenny A Hurcombe; Raina D Ramnath; Mark Graham; Philip A Lewis; Marieangela C Wilson; Kate J Heesom; Matthew J Butler; Rebecca M Perrett; Chris R Neal; Eleanor Herbert; Edward Mountjoy; Denize Atan; Viji Nair; Wenjun Ju; Robert G Nelson; Matthias Kretzler; Simon C Satchell; Craig A McArdle; Gavin I Welsh; Richard J M Coward Journal: Proc Natl Acad Sci U S A Date: 2020-06-19 Impact factor: 11.205