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Enhanced tissue polyamine content in the spontaneously hypertensive rat
J Ibrahim1, A D Hughes, M Schachter
1Department of Clinical Pharmacology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Summary
Polyamines like spermidine and spermine are elevated in the cardiovascular tissues of spontaneously hypertensive rats. Inhibiting polyamine synthesis with difluoromethylornithine (DFMO) did not lower blood pressure in this hypertension model.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pharmacology
Background:
- Endogenous polyamines regulate cellular growth and differentiation.
- Hypertension involves structural changes in the circulatory system, potentially influenced by polyamines.
Purpose of the Study:
- To investigate elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto (WKY) rats.
- To assess the impact of difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, on tissue polyamines and blood pressure in SHR and WKY rats.
Main Methods:
- SHR and WKY rats received either 2% DFMO or drug-free water.
- Blood pressure was monitored regularly.
- Tissue polyamine levels were analyzed post-treatment.
Main Results:
- Spermidine and spermine levels were significantly higher in the ventricles, resistance vessels, and liver of SHR compared to WKY rats.
- DFMO treatment reduced ventricular spermidine in SHR but did not alter polyamines in SHR resistance vessels or liver.
- DFMO did not affect the blood pressure of either SHR or WKY rats.
Conclusions:
- This study demonstrates elevated polyamine concentrations in the resistance vasculature of SHR for the first time.
- DFMO's limited effect on tissue polyamines suggests stringent regulation of polyamine homeostasis in this hypertension model, contrasting with other models.