REGULATION OF NEURONAL NITRIC-OXIDE SYNTHASE IN RAT ADRENAL-MEDULLA

Neuronal nitric oxide synthase (nNOS) has been suggested to be involve d in cardiovascular homeostasis. We studied the regulation of nNOS exp ression, determining nNOS mRNA expression levels in various tissues in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We also investigated the effects of antihypertensive treatment with the angiotensin II antagonist hydralazine or reserpine on nNOS mRNA expres sion. The expression levels of nNOS mRNA and nNOS protein were determi ned by Northern and Western blot analysis, respectively. NADPH-diaphor ase histochemistry was used to identify cells in the adrenal medulla t hat expressed nNOS. No significant differences in expression levels in SHR and WKY were observed in the cerebellum and brain stem. nNOS mRNA expression levels in the decapsular portion of the adrenal gland were developmentally modulated and in a 24-week-old WKY were 2.5 times hig her than in an age-matched SHR. This reduced expression of nNOS mRNA i n the decapsular portion of the adrenal gland of SHR seemed to be resu lt of hypertension in the SHR, because administration of either an ang iotensin II antagonist (TCV-116) or hydralazine upregulated nNOS mRNA expression in both SHR and WKY. Marked augmentation of nNOS mRNA expre ssion in the decapsular portion of the adrenal gland by reserpine trea tment suggested an intimate relation between nNOS in the decapsular po rtion of the adrenal gland and the sympathoadrenal system. Reserpine t reatment also increased the expression of nNOS protein; however, reser pine treatment did not affect the distribution pattern of nNOS-positiv e cells (NADPH-diaphorase-positive cells) in the adrenal medulla. The present results suggest that nNOS gene expression in the decapsular po rtion of the adrenal gland is not constitutive and that an intimate re lation may exist between nNOS in the decapsular portion of the adrenal gland and the sympathoadrenal system.