Eflornithine alters changes in vascular responsiveness associated with coarctation hypertension.
This study examined the temporal effects of the polyamine synthesis inhibitor eflornithine (alpha-difluoromethylornithine) on vascular responses to KCI, norepinephrine, sodium nitroprusside and acetylcholine in aortic rings from coarctation hypertensive rats. Coarctation hypertension reduced the contractile response of aortic rings to KCI and norepinephrine, increased sensitivity (reduced the EC50 value) to norepinephrine and attenuated relaxation to acetylcholine by 14 days of hypertension. Treatment of coarctation hypertensive rats with eflornithine resulted in a normalization of the contractile intensity to KCI and norepinephrine and relaxations to acetylcholine by 14 days of hypertension. Responses to sodium nitroprusside were similar in all groups at all time points. Hyperresponsiveness to norepinephrine produced by coarctation of the aorta was not affected by eflornithine. These studies indicate that normalization of vascular function can occur in the presence of significantly elevated blood pressure upon chronic administration of eflornithine. This functional normalization correlates with eflornithine-mediated regression of structural abnormalities normally associated with pressure overload hypertension.
Lipke
D W
DW
Division of Pharmacology and Experimental Therapeutics College of Pharmacy, University of Kentucky, Lexington, 40536, USA.
Newman
P S
PS
Tofiq
S
S
Aziz
S M
SM
Soltis
E E
EE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001017:Aortic Coarctation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D000518:Eflornithine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000037:antagonists & inhibitors*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D011189:Potassium Chloride; D000109:Acetylcholine; D009638:Norepinephrine; D000518:Eflornithine