title: Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats.
abstract: Neuropeptide Y (NPY), a sympathetic neurotransmitter, is highly associated with baroreflex dysfunction and multiple cardiac diseases such as diabetic myocardiopathy. In the present study, we aimed to explore the role of peripheral NPY Y1 receptor (Y1R) and Y2 receptor (Y2R), which are dominantly present in peripheral cardiovascular control, in baroreflex sensitivity (BRS) of streptozotocin (STZ)-induced diabetic rats. Peripheral Y1R and Y2R were antagonized by specific antagonists (BIBP 3226 and BIIE 0246, respectively) from subcutaneously implanted ALZET mini-osmotic pump in STZ-induced diabetic rats for 4 weeks. Then baseline systolic blood pressure, heart rate, cardiac function, BRS, plasma NPY and lipid levels were evaluated. We found that STZ led to increased plasma NPY and lipid level. And the STZ-increased lipid levels were reduced by BIBP 3226 and BIIE 0246. BIBP 3226 ameliorated the aberrant BRS, but had little effect on the impaired cardiac function of the STZ rats. BIIE 0246 alleviated sodium nitroprusside (SNP)-induced but not phenylephrine (PE)-induced aberrant baroreﬂex control of heart rate in the STZ rats. In addition, BIIE 0246 alleviated the bradycardia, but further impaired cardiac contractility in the STZ rats. These results suggest that peripheral Y1R and Y2R play different roles in STZ-induced impairment of BRS.
authors: Department of Pharmacology, Harbin Medical University, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin 150081, China. E-mail: aijing_86@yahoo.com.cn.
authors: Hui-Fang
authors: HF
authors: Niu
authors: Ling
authors: L
authors: Xu
authors: Yan
authors: Y
authors: Yan
authors: Fang
authors: F
authors: Xie
authors: Bao-Feng
authors: BF
authors: Yang
authors: Jing
authors: J
authors: Ai
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017704:Baroreflex; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure; D001919:Bradycardia; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate; D009200:Myocardial Contraction; D009478:Neuropeptide Y / Q000097:blood; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013311:Streptozocin
chemical_list: C092926:BIBP 3226; D001552:Benzazepines; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D013311:Streptozocin; D001120:Arginine; C403256:BIIE 0246