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Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats

NIU Hui-Fang, XU Ling, YAN Yan, XIE Fang, YANG Bao-Feng, AI Jing^*

Department of Pharmacology, Harbin Medical University, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin 150081, China

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.

Key words: Neuropeptide Y; baroreflex sensitivity; BIBP 3226; BIIE 0246; diabetes mellitus

Received: 　　Accepted:

Corresponding author: 艾静　　E-mail: aijing_86@yahoo.com.cn

Citing This Article：

NIU Hui-Fang, XU Ling, YAN Yan, XIE Fang, YANG Bao-Feng, AI Jing. Inhibition of peripheral NPY Y1 and Y2 receptors ameliorates the aberrant baroreceptor reflex sensitivity in streptozotocin induced diabetic rats. Acta Physiol Sin 2013; 65 (4): 370-380 (in Chinese with English abstract).