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(Hypertension. 2001;37:1164.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Decreased Renal Expression of Nitric Oxide Synthase Isoforms in Adrenocorticotropin-Induced and Corticosterone-Induced Hypertension

Yi-kun Lou; Cheng Wen; Ming Li; David J. Adams; Min-xia Wang; Feng Yang; Brian J. Morris; Judith A. Whitworth

From the Department of Physiology and Institute for Biomedical Research (Y.L., D.J.A., B.J.M.), and Department of Pathology (F.Y), Basic & Clinical Genomics Laboratory, Department of Medicine (C.W., M.L., M.W.), St George Hospital, The University of Sydney; and The John Curtain School of Medical Research (J.A.W.), Australian National University, Canberra (Australia).

Correspondence to Judith A. Whitworth, The John Curtain School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601, Australia. E-mail Director{at}JCSMR.anu.edu.au

Abstract—Administration of adrenocorticotropic hormone (ACTH) leads to the development of hypertension. Because glucocorticoids can affect the nitric oxide system at several sites, the present study tested the hypothesis that nitric oxide synthase (NOS) expression may be altered in ACTH-induced and corticosterone-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 corticosterone-treated and 10 control rats. In addition, in situ hybridization and immunohistochemistry were used to confirm changes by detection of Nos in RNA and NOS protein in tissues. Systolic blood pressure of ACTH and corticosterone rats was elevated (165±6 and 162±11 mm Hg; P<0.001 versus control). 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 Nos3, 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 cortex 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). Reductions seen in kidney were supported by in situ hybridization and immunohistochemistry. Apart from a 62±2% decrease in Nos2 mRNA in adrenal of ACTH 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 first time that the physiological components of glucocorticoid action (ACTH and corticosterone) when given chronically in vivo reduce Nos2 and Nos3 expression in the kidney. Such changes are consistent with a role in hypertension for ACTH and corticosterone.

Key Words: immunohistochemistry • hybridization • RNA • nitric oxide • isoenzymes • reverse transcriptase–polymerase chain reaction

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