The role of matrix metalloproteinases in vascular function: implications for normal pregnancy and pre-eclampsia.
OBJECTIVE
(1) To investigate the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation; (2) To investigate the role of matrix metalloproteinases (MMPs) in these parameters of vascular function.


METHODS
Analysis of the effects of plasma from non-pregnant, normal pregnant and pre-eclamptic women on myogenic tone and endothelium-dependent relaxation, and the effects of MMP inhibition on these parameters.


METHODS
University of Alberta, Edmonton, Alberta, Canada.


METHODS
Pooled plasma from non-pregnant (n= 9), normal pregnant (n= 6) and pre-eclamptic women (n= 12).


METHODS
Mesenteric arteries from virgin female C57BL/6J mice were exposed to pooled plasma from non-pregnant, normal pregnant and pre-eclamptic women in the absence and presence of GM6001 (5 microM; MMP inhibitor), and arterial function was assessed.


METHODS
Myogenic tone and endothelium-dependent relaxation.


RESULTS
Plasma of women with pre-eclampsia, and interestingly, plasma of non-pregnant women, significantly enhanced myogenic tone at pressures > or =70 mmHg (P < 0.001) and blunted the maximum relaxation to methacholine (P < 0.001; P < 0.005) in isolated arteries. GM6001 altered response only in vessels exposed to the plasma of women with pre-eclampsia; however, contrary to our hypothesis, this further enhanced myogenic tone and further abrogated relaxation.


CONCLUSIONS
The strikingly similar vascular function profiles of vessels incubated in the plasma of non-pregnant and pre-eclamptic women suggest that pre-eclampsia may be due, in part, to the lack of a necessary adaptation to pregnancy. Despite these similarities, however, there are differential effects of MMP inhibition, suggesting that MMPs play a greater role in the vasculature of women with pre-eclampsia compared with non-pregnant and normal pregnant women.
Merchant
Shaila J
SJ
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Davidge
Sandra T
ST
D000328:Adult; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009126:Muscle Relaxation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010949:Plasma; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology
D004151:Dipeptides; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases