LOWER THAN NORMAL EXPRESSION OF BRAIN NITRIC-OXIDE SYNTHASE GENE IN THE HYPOTHALAMUS OF DEOXYCORTICOSTERONE ACETATE SALT HYPERTENSIVE RATS

Objective To elucidate the role of brain nitric oxide produced by neur onal constitutive nitric oxide synthase in sodium-induced hypertension , Design and methods Diets containing a high (8% NaCl), a medium (2% N aCl), and a low (0.2% NaCl) sodium content were administered to Wistar rats aged 12 weeks for 10 days or 8 weeks until they were killed. Mal e Wistar rats administered either deoxycorticosterone acetate, 1% NaCl or both and the respective controls were killed 2 weeks (during prehy pertensive stage) or 6 weeks (during hypertensive stage) after the sta rt of treatment The hypothalamus and lower brainstem were excised for extraction of total RNA. Reverse transcription polymerase chain reacti ons of constitutive nitric oxide synthase messenger RNA and glyceralde hyde-3-phosphate dehydrogenase messenger RNA were performed, and const itutive nitric oxide synthase messenger RNA levels were expressed rela tive to glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels. Results A high sodium intake for 10 days tended to decrease constitut ive nitric oxide synthase messenger RNA levels in the hypothalamus, co mpared with effect of a low sodium intake, Constitutive nitric oxide s ynthase messenger RNA levels in the hypothalamus of deoxycorticosteron e acetate-salt hypertensive rats were lower than those in the control sham-operated rats. Neither alteration of sodium intake nor administra tion of deoxycorticosterone with and without sodium affected constitut ive nitric oxide synthase gene expression in the lower brainstem, Conc lusions Expression of neuronal constitutive nitric oxide synthase gene is downregulated in the hypothalamus of deoxycorticosterone acetate-s alt hypertensive rats. This lower than normal expression of neuronal c onstitutive nitric oxide synthase gene in the hypothalamus could be an adaptive response to sodium-induced hypertension, and suggests that n itric oxide produced by hypothalamic constitutive nitric oxide synthas e plays a role in maintenance of blood pressure in relation to sodium balance in rats. (C) 1998 Lippincott-Raven Publishers.