Decreased ornithine decarboxylase activity in the kidneys of Dahl salt-sensitive rats.
To assess the roles of polyamines (putrescine, spermidine, and spermine) and ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, in the development of salt-sensitive hypertension, we evaluated activity and expression of ODC, urinary polyamine excretion, and antizyme (endogenous ODC inhibitor protein) expression in Dahl salt-sensitive (SS) and salt-resistant (SR) rats after they were fed on a low (0.3%) or high (4%) salt diet for 4 weeks. We also examined the effects of spermidine and difluoromethylornithine (DFMO: a specific inhibitor of ODC) on the systolic blood pressure and ODC protein expression in SS rats fed a high salt diet. Renal ODC activity and urinary polyamine excretion in SS rats were lower than those in SR rats after 4 weeks treatment with a low or high salt diet. The renal ODC protein expression of SS rats was paradoxically increased as compared to the SR group. A high salt diet did not alter ODC activity but increased ODC protein only in SS rats. ODC mRNA and antizyme protein expressions were not significantly different among the four groups. Spermidine supplementation attenuated and DFMO exaggerated hypertension in SS rats fed a high salt diet. Spermidine down-regulated and DFMO up-regulated renal ODC protein in SS rats on a high salt diet. ODC activity was decreased but protein was paradoxically increased in kidneys of SS rats. ODC protein was suggested to increase in compensation for the inhibition of its activity. Impaired ODC activity and polyamine production in the kidney may exaggerate salt-sensitive hypertension in SS rats.
Hayashi
Takeshi
T
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Tsujino
Takeshi
T
Iwata
Sachiyo
S
Nonaka
Hidemi
H
Emoto
Noriaki
N
Yano
Yoshihisa
Y
Otani
Shuzo
S
Hayashi
Yoshitake
Y
Itoh
Hiroshi
H
Yokoyama
Mitsuhiro
M
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D015971:Gene Expression Regulation, Enzymologic; D006339:Heart Rate; D006977:Hypertension, Renal / Q000201:enzymology* / Q000473:pathology / Q000652:urine; D007668:Kidney / Q000201:enzymology*; D008297:Male; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism*; D011073:Polyamines / Q000652:urine; D051381:Rats; D020303:Rats, Inbred Dahl
D011073:Polyamines; D009955:Ornithine Decarboxylase