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Decreased ornithine decarboxylase activity in the kidneys of Dahl salt-sensitive rats
Takeshi Hayashi1, Takeshi Tsujino, Sachiyo Iwata
1Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
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.
Insights
Impaired kidney ornithine decarboxylase (ODC) activity and polyamine production contribute to salt-sensitive hypertension in Dahl SS rats. Spermidine supplementation helped, while ODC inhibition worsened hypertension.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Biochemistry
Background:
- Polyamines and ornithine decarboxylase (ODC) are crucial for cell growth and function.
- Salt-sensitive hypertension is a complex condition with poorly understood mechanisms.
- Dahl salt-sensitive (SS) rats are a model for studying salt-sensitive hypertension.
Purpose of the Study:
- To investigate the role of polyamines and ODC in the development of salt-sensitive hypertension in Dahl SS rats.
- To examine the effects of dietary salt, spermidine, and ODC inhibition on blood pressure and ODC expression.
Main Methods:
- Dahl SS and salt-resistant (SR) rats were fed low or high salt diets for 4 weeks.
- Assessed renal ODC activity and protein expression, urinary polyamine excretion, and antizyme expression.
- Administered spermidine or difluoromethylornithine (DFMO) to SS rats on a high salt diet.
Main Results:
- SS rats exhibited lower renal ODC activity and polyamine excretion than SR rats.
- Renal ODC protein was paradoxically increased in SS rats, especially on a high salt diet.
- Spermidine attenuated hypertension, while DFMO exacerbated it in SS rats.
Conclusions:
- Reduced ODC activity and polyamine production in the kidney may contribute to salt-sensitive hypertension.
- Increased ODC protein in SS rats might be a compensatory response to inhibited activity.
- Targeting polyamine synthesis could be a therapeutic strategy for salt-sensitive hypertension.
