Preserved tissue-type plasminogen activator release and endothelium-dependent vasodilation in postmenopausal women with NIDDM

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.