Decreased renal expression of nitric oxide synthase isoforms in adrenocorticotropin-induced and corticosterone-induced hypertension

Administration of adrenocorticotropic hormone (ACTH) leads to the developme nt of hypertension. Because glucocorticoids can affect the nitric oxide sys tem at several sites, the present study tested the hypothesis that nitric o xide synthase (NOS) expression may be altered in ACTH-induced and corticost erone-induced hypertension in the rat. This was addressed by measuring Nos1 , Nos2, and Nos3 mRNA in the kidney, adrenal gland, heart, and hypothalamus of 16 ACTH-treated and 16 vehicle-treated rats as well as in 10 corticoste rone-treated and 10 control rats. In addition, in situ hybridization and im munohistochemistry were used to confirm changes by detection of Nos in RNA and NOS protein in tissues. Systolic blood pressure of ACTH and corticoster one rats was elevated (165 +/-6 and 162 +/- 11 mm Hg; P <0.001 versus contr ol). Each Nos isoform mRNA was measured by reverse transcriptase-polymerase chain reaction technique. In ACTH rats, mRNA for Nos2 was reduced in renal cortex by 58 +/-5% and in medulla by 68 +/-7%; for Nod, mRNA reductions of 59 +/-6% and 51 +/- 11% were seen (P <0.001 after Hochberg correction for multiple comparisons). In corticosterone rats, Nos2 mRNA decreased in corte x by 68 +/-5% and in medulla by 62 +/-6%; Nos3 MRNA by 50 +/-8% in cortex, and Nos1 by 29 +/-7% in medulla (all P <0.001 after Hochberg correction). R eductions seen in kidney were supported by in situ hybridization and immuno histochemistry. Apart from a 62 +/-2% decrease in Nos2 mRNA in adrenal of A CTH rats (corrected P <0.05), no significant changes were seen in the other nonrenal tissues for any isoform. In conclusion, we have shown for the fir st time that the physiological components of glucocorticoid action (ACTH an d corticosterone) when given chronically in vivo reduce Nos2 and Nos3 expre ssion in the kidney. Such changes are consistent with a role in hypertensio n for ACTH and corticosterone.