Eflornithine treatment in SHR: potential role of vascular polyamines and ornithine decarboxylase in hypertension.
This study was performed to assess the potential role of polyamines in the alterations in vascular structure and function in spontaneously hypertensive rats (SHR). The effects of chronic administration of eflornithine (alpha-difluoromethylornithine; DFMO), a highly specific inhibitor of ornithine decarboxylase (the rate limiting enzyme in polyamine biosynthesis), on vascular polyamine contents, vascular structure and function, and blood pressure was studied. Male SHR (16-17 weeks of age) with an average systolic blood pressure (SBP) of 161 +/- 3 mmHg were used. The rats were divided into two groups and received either tap water or a 1% DFMO solution to drink for 6 weeks. SBP and body weight were recorded prior to and once-a-week during the experiment. Standard in vitro vascular reactivity studies on ring segments of aorta and tail artery were performed. Ring segment weight, arterial medial thickness, and vascular polyamine contents were also determined. Body weights were not significantly affected by the DFMO treatment. SBP in control SHR rose progressively to an average value of 185 +/- 5 mmHg by the sixth experimental week. Although DFMO treatment did not cause a significant decrease in SBP compared to pretreatment values, it did prevent a further increase in SBP. Aortic and tail artery responsiveness to norepinephrine and electrical stimulation, respectively, ring segment weight, arterial medial thickness, and vascular polyamine contents were all significantly less in SHR receiving the DFMO treatment. These data are the first to demonstrate the effectiveness of DFMO to lower polyamine contents in the vasculature of hypertensive SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
E E
EE
Soltis
P S
PS
Newman
J W
JW
Olson
D000818:Animals; D015317:Biogenic Polyamines / Q000145:classification / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000518:Eflornithine / Q000627:therapeutic use*; D004558:Electric Stimulation; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D009955:Ornithine Decarboxylase / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D013268:Stimulation, Chemical
D015317:Biogenic Polyamines; D009955:Ornithine Decarboxylase; D000518:Eflornithine