Related Experiment Videos
Polyamines, vascular smooth muscle, and deoxycorticosterone acetate-salt hypertension
E E Soltis1, P S Newman, J W Olson
1Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Abstract:
This study was performed to determine if an alteration in vascular polyamine contents is associated with the development of deoxycorticosterone acetate-salt hypertension. The effects of chronic administration of alpha-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase and thus polyamine biosynthesis, on vascular polyamine contents, structure, and function as well as the development of hypertension was studied. Control and deoxycorticosterone acetate-salt rats received either tap water or a drinking solution containing alpha-difluoromethylornithine for 6 weeks, during which period systolic blood pressures were recorded. Vascular reactivity studies were performed on rings of aorta and tail artery. Medial thickness, vessel weight, and vascular polyamine contents were also assessed in these arteries. alpha-difluoromethylornithine treatment had no significant effect on either systolic blood pressure or vascular structure, function, and polyamine contents of control animals. The elevation in blood pressure and the increase in medial thickness, ring weight, and vascular polyamine contents as well as altered vascular reactivity observed in deoxycorticosterone acetate-salt rats was significantly attenuated by alpha-difluoromethylornithine treatment. These results are the first to demonstrate that vascular polyamine contents are elevated in the deoxycorticosterone acetate-salt rat and that chronic alpha-difluoromethylornithine treatment prevents the rise in vascular polyamines as well as the elevation in blood pressure and attendant changes in the vasculature. Thus, the increase in vascular polyamines may comprise a critical link between the initiating stimuli and the alterations in vascular structure and function implicated in the pathogenesis of deoxycorticosterone acetate-salt hypertension.
Insights
Elevated vascular polyamines contribute to deoxycorticosterone acetate-salt hypertension. Inhibiting polyamine synthesis with alpha-difluoromethylornithine reduced blood pressure and vascular changes in rats.
Area of Science:
- Cardiovascular Research
- Biochemistry
- Pharmacology
Background:
- Deoxycorticosterone acetate-salt (DOCA-salt) hypertension is a model characterized by elevated blood pressure and vascular remodeling.
- The role of polyamines, crucial for cell growth and differentiation, in the pathogenesis of hypertension is not fully understood.
Purpose of the Study:
- To investigate the association between vascular polyamine content and the development of DOCA-salt hypertension.
- To evaluate the effects of inhibiting polyamine biosynthesis on hypertension-induced vascular changes.
Main Methods:
- Rats were subjected to DOCA-salt treatment with or without alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor.
- Systolic blood pressure, vascular reactivity, medial thickness, vessel weight, and polyamine content were assessed.
- Control groups received DFMO or vehicle only.
Main Results:
- DOCA-salt rats exhibited increased blood pressure, medial thickness, vessel weight, and vascular polyamine content.
- DFMO treatment significantly attenuated these hypertension-induced changes in DOCA-salt rats.
- DFMO had no significant effects on normotensive control rats.
Conclusions:
- Vascular polyamine levels are elevated in DOCA-salt hypertension.
- Inhibition of polyamine biosynthesis effectively prevents the development of hypertension and associated vascular alterations.
- Increased vascular polyamines represent a key factor linking hypertension stimuli to vascular pathology.