Author + information
- Received October 19, 1995
- Revision received January 4, 1996
- Accepted January 23, 1996
- Published online June 1, 1996.
- Sujata Basu, MSc,
- Sunil K. Sinha, BSc,
- Qiming Shao, MD,
- Pallab K. Ganguly, MD∗ and
- Naranjan S. Dhalla, PhD,MD(Hons),FACC
- ↵∗Address for correspondence Dr. Pallab K. Ganguly, Department of Anatomy, Faculty of Medicine, University of Manitoba, 730 William Avenue, Winnipeg, Manitoba, Canada R3E OW3.
Objectives. We examined the possible effect of neuropeptide Y in modulating central sympathetic activity after myocardial infarction in rats.
Background. Previous studies have shown the coexistence of neuropeptide Y and norepinephrine in the brain and a possible functional interaction between the two. Neuropeptide Y inhibits the release of norepinephrine at the presynaptic level and can be considered to act as a neuromodulator.
Methods. Two groups of rats were examined in this study—an experimental group, defined as those rats undergoing left coronary artery ligation, and a sham group without coronary artery ligation, serving as the control group. The animals in both groups underwent microdialysis in the paraventricular nucleus at 2, 4 and 8 weeks after operation. Microdialysis samples were collected with and without injecting neuropeptide Y in the paraventricular nucleus. The concentration of norepinephrine was determined by injecting purified microdialysate samples during high performance liquid chromatography. To explore the receptor's possible role, autoradiographic localization of neuropeptide Y receptors in the paraventricular nucleus was also carried out in the experimental and sham groups.
Results. The concentration of norepinephrine measured in the samples was decreased by 50% with neuropeptide Y in 2− and 4-week old rats after infarction. but by only 20% (p < 0.05) in 8-week old rats after infarction. The diminished inhibitory effects of neuropetide Y on norepinephrine release was associated with increased sympathetic activity, as reflected by plasma norepinephrine; 8-week old rats after infarction had almost a 100% (p < 0.05) increase in their plasma norepinephrine level compared with the sham group. Autoradiography revealed a significant decrease in density of neuropeptide Y receptors in the paraventricular nucleus in 8-week old rats after infarction (p < 0.05).
Conclusions. The data presented in this report suggest that the reduction of the inhibitory activation of neuropeptide Y on sympathetic release may contribute to elevated norepinephrine levels after myocardial infarction.
☆ This study was supported by the MRC Group in Experimental Cardiology, Medical Research Council of Canada, Ottawa, Ontario (Dr. Dhalla); the Paul H. T. Thoralakson Foundation, Winnipeg (Dr. Ganguly); and the Heart and Stroke Foundation of Manitoba, Winnipeg (Dr. Ganguly).
- Received October 19, 1995.
- Revision received January 4, 1996.
- Accepted January 23, 1996.