Brain nitric oxide synthase messenger RNA in central mineralocorticoid hypertension.
The mechanism underlying the central hypertensinogenic effects of mineralocorticoids remains unclear. Given that nitric oxide (NO) is thought to act at autonomic sites in the brain to regulate arterial blood pressure, the effects of the potent mineralocorticoids aldosterone and 19-noraldosterone on the abundance of neuronal NO synthase (nNOS) mRNA in the brain were investigated. Wistar-Kyoto rats received a continuous intracerebroventricular infusion of aldosterone or 19-noraldosterone (5 ng/h) from an implanted osmotic minipump for 4 weeks. Total RNA was purified from microdissected tissue blocks containing the hypothalamus, dorsal medulla, rostral ventrolateral medulla, or caudal ventrolateral medulla, and changes in the abundance of nNOS mRNA were determined with a semiquantitative competitive polymerase chain reaction method. Blood pressure was significantly increased in rats 2, 3, and 4 weeks after the onset of intracerebroventricular aldosterone or 19-noraldosterone infusion compared with that in animals receiving vehicle. Subcutaneous infusion of either mineralocorticoid had no effect on blood pressure. Compared with controls, rats treated with aldosterone or 19-noraldosterone for 4 weeks showed significant decreases in the amount of nNOS mRNA in the hypothalamus and rostral and caudal ventrolateral medulla. These data suggest that reduced nNOS activity may contribute to the increase in blood pressure in rats with central mineralocorticoid-induced hypertension.
Takeda
Y
Y
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Izumigaoka, Japan.
Miyamori
I
I
Yoneda
T
T
Furukawa
K
K
Inaba
S
S
Takeda
R
R
Mabuchi
H
H
D000450:Aldosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007276:Injections, Intraventricular; D008901:Mineralocorticoids; D019001:Nitric Oxide Synthase / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D012016:Reference Values
D008901:Mineralocorticoids; D012333:RNA, Messenger; D000450:Aldosterone; C027514:19-noraldosterone; D019001:Nitric Oxide Synthase