Renal sympathetic nerve activation in relation to reserpine-induced depletion of neuropeptide Y in the kidney of the rat


Department of Pharmacology, Karolinska Institutet, Box 60400, S-104 01 Stockholm, Sweden


The effect of reserpine treatment on renal sympathetic nerve activity and tissue levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and noradrenaline (NA) were studied in rats. Injection of reserpine (I mg kg-1 i. v.) caused a clear-cut (about 50%) increase in rectified activity of the post-ganglionic sympathetic nerves to the kidney within 15 min in chloralose-anaesthetized rats compared to a saline-treated control group. This increase in nerve activity was still maintained 120 min after the reserpine injection. The renal nerve activation was accompanied by a progressive fall in mean arterial blood pressure and an initial tachycardia. In a separate group of conscious rats, the levels of NPY-LI (1.3 ± 0.06 pmol g-1) and NA (1.6 ± 0.07 nmol g-1) in the kidney were significantly reduced (by 74 and 83 %, respectively) 24 h after reserpine treatment (I mg kg-1 i. v.). The reserpine-induced depletion of NPY-LI, but not that of NA, was inhibited by pretreatment with the ganglionic blocking agent chlorisondamine or the alpha2-adrenoceptor agonist clonidine, both of which are known to decrease renal sympathetic nerve activity. The tissue content of NPY-LI in the right atrium (16.3 ± 0.7 pmol g-1) was not reduced by reserpine. Arterial plasma NPY-LI in the rat was high (222 ± 5 pmol l-1), and this value did not change after pretreatment with reserpine, chlorisondamine or clonidine, indicating that, in the rat, circulating NPY-LI is not a good indicator of sympatho-adrenal activity. In conclusion, reserpine treatment is associated with an increase in the renal sympathetic nerve activity, which might be a factor contributing to a depletion of NPY-LI from sympathetic nerve endings, while the depletion of NA seems to be less dependent on the nerve activity. It is also likely that increased release of NPY-LI per nerve impulse, due to lack of alpha-adrenergic auto-inhibition of release after depletion of NA, contributes to the renal depletion of NPY-LI.