K. Manhem et al., Preserved tissue-type plasminogen activator release and endothelium-dependent vasodilation in postmenopausal women with NIDDM, J DIABET C, 14(3), 2000, pp. 127-134
We have recently shown that the net release of tissue-type plasminogen acti
vator (t-PA) antigen can be rapidly enhanced by the muscarinic receptor sti
mulation in healthy males. Since diabetes mellitus has been associated with
endothelial dysfunction, the aim of the present study was to compare the e
ndothelium-derived local net release of t-PA with vasodilation in response
to muscarinic receptor stimulation by metacholine (Mch) and fluid shear str
ess in a group of postmenopausal women with non-insulin-dependent diabetes
mellitus (NIDDM), and to elucidate the influence of estrogen on this proces
s. Six postmenopausal women with NIDDM were in randomized order exposed to
stepwise intra-arterial infusions of Mch (0.1-0.8-4.0 mu g/min) and nitropr
usside (SNP; 0.5-2.5-10.0 mu g/min). Forearm blood flow (FBF) was assessed
by plethysmography. The infusions with Mch and SNP were repeated during sim
ultaneous intra-arterial infusion of 17-beta estradiol (E; 20 ng/min). Duri
ng placebo infusion, FBF increased significantly in response to Mch and SNP
(p < 0.001), but no differences between Mch and SNP were found. In paralle
l to the blood flow increase in response to Mch stimulation, the t-PA net r
elease was increased over 30 times (p ( 0.001). Estrogen did not produce an
y change in blood flow or net release oft-PA at baseline or in response to
either drug (Mch or SNP). The present study demonstrates a preserved endoth
elium-dependent vasodilation and stimulated tissue-type plasminogen activat
or release in NIDDM postmenopausal women in response to Mch stimulation. Ac
ute intra-arterial infusion of 17-beta estradiol did not affect the vasodil
ation or the t-PA net release. (C) 2000 Elsevier Science Inc. All rights re
served.