Enhanced tissue polyamine content in the spontaneously hypertensive rat.
1. Endogenous polyamines play a key role in mediating cellular growth and differentiation. Hypertension is associated with structural modifications of the circulatory system, a process that may be facilitated by polyamines. In this study, we examined whether there are elevated polyamine concentrations in the cardiovascular tissues of spontaneously hypertensive rats (SHR) relative to Wistar-Kyoto (WKY) rats. We also determined the chronic effect of 2% difluoromethylornithine (DFMO; a polyamine biosynthesis inhibitor) on tissue polyamines and hypertension. 2. SHR and WKY rats were treated with either 2% DFMO or drug-free drinking water; blood pressure was measured on alternate days and tissue polyamines were analysed at the end of the study. 3. We found that spermidine and spermine concentrations were markedly raised in the ventricles, resistance vessels and liver of the SHR, in comparison with corresponding tissues of WKY rats. DFMO did not affect SHR resistance vessel and liver polyamines, although spermidine in the ventricles was reduced. The blood pressure of neither SHR nor WKY rats was affected by DFMO. 4. In conclusion, this study shows for the first time a raised concentration of polyamines in the resistance vasculature of the SHR, in relation to their normotensive counterparts. The inability of DFMO to significantly reduce tissue polyamines in this study is in contrast to the effectiveness of 2% DFMO in other hypertension models, suggesting that polyamine homeostasis in this model may be stringently regulated.
Ibrahim
J
J
Department of Clinical Pharmacology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Hughes
A D
AD
Schachter
M
M
Sever
P S
PS
D000818:Animals; D001808:Blood Vessels / Q000737:chemistry; D002319:Cardiovascular System / Q000737:chemistry*; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008297:Male; D011073:Polyamines / Q000032:analysis* / Q000037:antagonists & inhibitors*; D011700:Putrescine / Q000032:analysis / Q000037:antagonists & inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013095:Spermidine / Q000032:analysis / Q000037:antagonists & inhibitors; D013096:Spermine / Q000032:analysis / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D011073:Polyamines; D013096:Spermine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine