Effects of anti-androgen treatment on the catecholamine synthetic pathway in the adrenal medulla of spontaneously hypertensive rats.
We investigated the effects of the antiandrogen flutamide on the activity of tyrosine hydroxylase, the levels of its encoding mRNA, and catecholamine levels in the adrenal medulla of male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flutamide (30 mg/kg) was administered subcutaneously daily (between 9 and 15 weeks of age). The systolic blood pressure of flutamide-treated SHR rats was lower than that of control SHR. Epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and the levels of encoding mRNA in the adrenal medulla were significantly lower in flutamide-treated SHR rats than in paired controls. Systolic blood pressure, epinephrine and norepinephrine levels, tyrosine hydroxylase activity, and encoding mRNA in the adrenal medulla of WKY rats showed no significant differences between flutamide-treated and control groups. These findings suggested that flutamide may have cardiovascular effects through alteration of the catecholamine synthetic pathway caused by removal of androgen receptor stimulation on the expression of tyrosine hydroxylase in the adrenal medulla of male SHR rats.
Kumai
T
T
Department of Pharmacology, St. Marianna University School of Medicine, Kanagawa, Japan.
Tanaka
M
M
Tateishi
T
T
Watanabe
M
M
Nakura
H
H
Asoh
M
M
Kobayashi
S
S
D000199:Actins / Q000096:biosynthesis; D000313:Adrenal Medulla / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000096:biosynthesis*; D004837:Epinephrine / Q000378:metabolism; D005485:Flutamide / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000378:metabolism
D000199:Actins; D000726:Androgen Antagonists; D002395:Catecholamines; D012333:RNA, Messenger; D005485:Flutamide; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine; D004837:Epinephrine