U073579.pdf (22.14 MB)
The role of the vascular endothelium in experimental and genetic hypertension.
thesisposted on 2015-11-19, 08:49 authored by Michael A. Bennett
These experiments have investigated how the endothelium modulates resistance artery contractility in hypertension. Mesenteric resistance arteries were mounted in a myograph for measurements of morphology and reactivity. In normal arteries the release of endothelial-derived relaxing and contracting factors plays an important role in modulating contractility and the balance between the two types of endothelial vasoactive substances may regulate resistance vessel tone. There was no difference in the contraction of arteries from two-kidney, one clip (2-K, 1C) hypertensive rats studied after 4 or 10 weeks duration compared to sham rats. Endothelial modulation was similar in both sets of arteries, suggesting that the endothelium does not mask an increased reactivity in 2-K, 1C hypertension. Contractile responses were increased in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto (WKY) controls. Inhibition of nitric oxide synthesis potentiated the contractile response in both sets of arteries, indicating that an alteration in endothelial modulation does not play a role in the enhanced reactivity in the SHR. In 2-K, 1C hypertension, endothelial dysfunction occurred as a result of a prolonged exposure to high blood pressure. This endothelial dysfunction is caused by the concomitant release of a contracting factor. Treatment of 2-K, 1C hypertensive rats with an angiotensin converting enzyme (ACE) inhibitor lowered blood pressure and caused a regression of cardiovascular structural alterations. Treatment also prevented the development of impaired endothelium-dependent relaxation. Treatment of SHRs with either an ACE inhibitor, a vasodilator or a calcium antagonist prevented the rise in blood pressure and normalised vascular structural alterations. There was a positive correlation between blood pressure and vascular structure, suggesting that blood pressure is a major determinant of vascular structure. Only ACE inhibitor treatment normalised resistance vessel contractility and endothelium-dependent relaxation suggesting that factors other than blood pressure reduction play an important role in restoring resistance artery endothelial function.
Date of award1995-01-01
Author affiliationCollege of Medicine, Biological Sciences and Psychology
Awarding institutionUniversity of Leicester