Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH

The role of nitric oxide in the regulation oi adrenal steroidogenesis was examined in BALB/c mice by employing the nitric oxide synthase inhibitors N-G-nitro L-arginine methyl ester (L-NAME) and N-G-nitro L-arginine (L-NNA). The administration of a single dose of nitric oxide inhibitors (50 mg kg(-1) body wt, i.p.) induced a fourfold increase in plasma corticosterone. Treatment with L-arginine (750 mg kg(-1) body wt, s.c.), but not D-arginine. completely prevented corticosterone increases induced by L-NAME. To analyse whether the activation of adrenal steroidogenesis induced by nitric oxide synthase inhibitors involved the stimulation of the hypothalamo-pituitary-ad renal axis. ACTH levels were assessed. It was found that L-NAME significantly enhanced plasma ACTH concentrations. Genetic variations in this regulatory pathway are suggested by the fact that L-NAME increased corticosterone levels in BALB/c, C3H/He and DBA-2 mice. but not in C57Bl/c mice, a strain characterized by a low steroid response to stress.