Selective peripheral regulation of noradrenaline and adrenaline release by nitric oxide

Abstract

1. Nitric oxide (NO) has complex effects on the sympatho-adrenal and cardiovascular systems and may act at both central and peripheral loci. Nitric oxide appears to act directly on blood vessels and indirectly by modulating the sympatho-adrenal system. In the present study, we investigated the contribution of catecholamine release from peripheral vascular and adrenal sympathetic nerves to the cardiovascular effects of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg). Our experiments were perfomed in pithed vagotomized rats to remove the influence of central and baroreflex pathways. 2. Spinal cord stimulations for 30 s periods at 1, 2, 5 and 10 Hz using pulses of 1 msec at 10 V caused marked increases in plasma adrenaline and noradrenaline. NG-Nitro-L-arginine methyl ester did not alter resting plasma catecholamine concentrations. However, L-NAME generally more than doubled stimulation-evoked release of adrenaline while reducing the extent of noradrenaline release relative to vehicle (saline)-treated controls. 3. NG-Nitro-L-arginine methyl ester significantly enhanced the vasopressor responses to spinal cord stimulation. The α1-adrenoceptor antagonist prazosin (0.2 mg/kg) reduced the pressor responses of electrically stimulated L-NAME-treated rats to levels below those of vehicle-treated control rats. 4. In the absence of electrical stimulation, L-NAME raised the blood pressure of pithed rats without altering plasma catecholamines and the pressor effect was briefly attenuated by L-arginine, but was unaffected by prazosin. 5. We conclude that the augmented pressor response to sympathetic stimulation in L-NAME-treated pithed rats is due largely to enhanced adrenal adrenaline release mediated by a peripheral mechanism. Stimulation of α1-adrenoceptors plays a major role in the pressor response to electrical stimulation of L-NAME-treated rats, but this is not due to L-NAME augmentation of noradrenaline release from vascular sympathetic nerves.