Altered neuropeptide Y effects on noradrenaline levels in the paraventricular nucleus of rats following aortic constriction.

OBJECTIVE

To clarify whether central catecholamine systems are modulated by neuropeptide Y (NPY) soon after imposing an increased pressure overload on the heart. Recent evidence supports the view that the sympathetic nervous system actively participates in the development of cardiac hypertrophy. Since noradrenaline-containing neurons involved with cardiovascular regulation within the brain are known to coexist with NPY, it is possible that a functional interaction between NPY and noradrenaline exists centrally.

DESIGN

The paraventricular nucleus (PVN) of aortic-banded Sprague-Dawley rats were sampled for noradrenaline levels using in vivo microdialysis and compared with samples taken from sham-operated controls. Autoradiographical localization of NPY receptors in the PVN was also carried out between animal groups.

ANIMALS

Forty-eight Sprague-Dawley rats (weighing between 175 and 200 g).

INTERVENTIONS

The 48 rats were randomly divided into two groups. One group underwent abdominal suprarenal aortic constriction. The control group underwent the same procedure without being banded. At 14 days postsurgery, the animals had microdialysis probes stereotaxically implanted into the PVN under anesthesia. A solution of NPY (10(-8) M) was perfused through the probe for 20 mins, and catecholamine levels were measured in the resulting perfusate.

MAIN RESULTS

Extracellular noradrenaline concentrations in the PVN were found to be increased following aortic constriction compared with sham controls (P < 0.05). Infusion of NPY resulted in a reduction of noradrenaline concentration in sham animals (P < 0.05), whereas no change in noradrenaline concentration was evident in the aortic-constricted group. Autoradiography of NPY receptors in the PVN showed a significant decrease in the receptor density in aortic-constricted rats versus sham controls (P < 0.05).

CONCLUSIONS

The results strongly support the view that NPY plays an important neuromodulatory role in the PVN regarding control of sympathetic output. It is suggested that cardiac hypertrophy may be precipitated secondary to changes in brain NPY levels and increased sympathetic activity.