Modulation of sympathetic activity by brain neuropeptide Y in cardiac hypertrophy.

Several observations now support the view that the sympathetic system actively participates in the development of cardiac hypertrophy. Since norepinephrine (NE)-containing neurons involved in cardiovascular regulation in the brain are known to coexist with neuropeptide Y (NPY), it is possible that a functional interaction between NPY and NE exists centrally. In an effort to clarify whether or not central catecholamine systems are modulated by NPY soon after imposing an increased pressure overload on the heart, male Sprague-Dawley rats underwent aortic constriction and were examined 14 days later. Rats were anesthetized and subjected to microdialysis sampling by stereotaxically implanting a probe into the caudal ventrolateral medulla (A1). Perfusate was collected after a 1-hour stabilization period, purified, and analyzed for interstitial concentrations of NE and other catecholamines using high-performance liquid chromatography with an electrochemical detector. Extracellular NE concentrations in the A1 area were found to be decreased. These results were associated with increased rate of change in the specific activity of NE (NE turnover) in heart, indicating increased sympathetic activity and an increased left ventricular weight. Also, infusion of NPY (10(-9) mol/L) by microdialysis in the A1 area resulted in the reduction of NE concentration; epinephrine and dopamine levels were also decreased. In contrast, methionine-enkephalin, another neuropeptide, had no effect on the extracellular catecholamine concentrations in the A1 area. Since neurons of the A1 group project almost exclusively to forebrain structures inhibiting sympathetic activity, it is concluded that decreases of NE and other catecholamines in afferent pathways regulating the caudal ventrolateral medulla may lead to an enhanced sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)