Effects of nitric oxide synthase inhibitor on tyrosine hydroxylase mRNA in the adrenal medulla of spontaneously hypertensive and Wistar Kyoto rats.
We studied the effects of N(G)-nitro-l-arginine methyl ester (L-NAME) on catecholamine levels, tyrosine hydroxylase (TH) activity, and TH mRNA levels in the adrenal medulla of spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). L-NAME (100 mg/L in drinking water) and atropine (10 mg/L in drinking water) were administered for 2 weeks. Epinephrine and norepinephrine levels, TH activity, and TH mRNA levels in the adrenal medulla of L-NAME-treated WKY were significantly decreased. These parameters were not significantly altered in the adrenal medulla of L-NAME-treated SHR. Nitrite/nitrate levels in the adrenal medulla of L-NAME-treated WKY were significantly decreased; however, no significant change in L-NAME-treated SHR was observed. Ca(2+)-dependent nitric oxide synthase (NOS) activity in the adrenal medulla of SHR was significantly decreased compared to that of WKY. TH mRNA levels in L-NAME + atropine-treated and L-NAME-treated WKY were significantly lower than TH mRNA levels in control WKY. These results suggest that nitric oxide in the adrenal medulla may enhance the catecholamine biosynthetic pathway via increased TH mRNA expression. Our results also suggest that this effect is suppressed in SHR due to decreased NOS activity in the adrenal medulla.
Kumai
T
T
Department of Pharmacology, Department of Pediatrics, St. Marianna University School of Medicine, 2-16-1 Sugao, Kanagawa, Miyamae-ku, 216-8511, Japan. yakuri@marianna-u.ac.jp
Asoh
K
K
Tateishi
T
T
Tanaka
M
M
Watanabe
M
M
Kobayashi
S
S
D000313:Adrenal Medulla / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004837:Epinephrine / Q000032:analysis*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000032:analysis; D009638:Norepinephrine / Q000032:analysis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D001285:Atropine; D019001:Nitric Oxide Synthase; D014446:Tyrosine 3-Monooxygenase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D004837:Epinephrine