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Transient involvement of endothelin in hypertrophic remodeling of small arteries
- Source :
- Journal of hypertension. 19(10)
- Publication Year :
- 2001
-
Abstract
- OBJECTIVE This study was designed to evaluate the capacity of norepinephrine (NE) to induce hypertrophic remodeling of small arteries in rats, and to determine the involvement of endothelin (ET) to initiate and maintain it. DESIGN AND RESULTS Treatment with NE (2.5 microg/kg per min) for 14 or 28 days produced a similar inward hypertrophic remodeling, characterized by a smaller lumen, but increased media thickness and cross-sectional area. Arterial stiffness was reduced. Histological evaluation confirmed the hypertrophic nature of remodeling. Concomitant administration of LU135252 (ET-receptor antagonist) for the first 14 days of NE administration prevented the development of hypertrophy, without altering arterial mechanics. Treatment with the same antagonist from day 14 to day 28 of NE or angiotensin II (Ang II) treatment failed to regress established vascular hypertrophy. In contrast, normalization of arterial structure was observed with prazosin, an alpha-adrenergic blocker. Endothelin content in small mesenteric arteries showed a transient elevation following chronic NE administration. CONCLUSIONS Increased circulating NE levels are associated with hypertrophic remodeling of small arteries, in which ET plays an initiating role. However, the maintenance of vascular hypertrophy is ET-independent, either in the presence of augmented circulating levels of NE or Ang II. Thus, early rather than late treatment with ET-receptor antagonists may be a preferable approach to limit small artery-mediated end-organ damage in cardiovascular diseases.
- Subjects :
- Endothelin Receptor Antagonists
medicine.medical_specialty
Time Factors
Physiology
Muscle hypertrophy
Rats, Sprague-Dawley
Norepinephrine
Internal medicine
Renin–angiotensin system
Internal Medicine
medicine
Prazosin
Animals
Mesenteric arteries
Endothelin-1
Phenylpropionates
business.industry
Angiotensin II
Endothelins
Hypertrophy
medicine.disease
Mesenteric Arteries
Rats
medicine.anatomical_structure
Endocrinology
Pyrimidines
Arterial stiffness
Vascular Resistance
Cardiology and Cardiovascular Medicine
Endothelin receptor
business
Artery
medicine.drug
Subjects
Details
- ISSN :
- 02636352
- Volume :
- 19
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of hypertension
- Accession number :
- edsair.doi.dedup.....9ac77a96046a89f308aebd6749f0fe03