Endothelium-dependent vasodilation and tissue-type plasminogen activator release in borderline hypertension

Abstract

We recently showed that muscarinic receptor stimulation causes a marked increase in the net release of tissue-type plasminogen activator (TPA) antigen and activity across the human forearm in vivo, in conjunction with endothelium-dependent vasodilation. Because hypertension has been associated with endothelial dysfunction, the aim of the study was to compare forearm TPA release and vasodilation in response to muscarinic stimulation in normotensive (NC) and borderline hypertensive (BH) subjects. The study was performed in 10 apparently healthy young men with BH and 10 male NC subjects. Methacholine (MCh: 0.1, 0.8, and 4.0 μg/min) and sodium nitroprusside (SNP: 0.5, 2.5, and 10 μg/min) were administered in randomized order as double- blind, stepwise, intrabrachial artery infusions. Forearm blood flow was assessed by plethysmography. Net release/uptake was calculated as the product of the arteriovenous concentration gradient and forearm plasma flow. Vasodilator responses to MCh were similar in both groups (P=NS), whereas the decrease in forearm vascular resistance in response to SNP was somewhat less in BH subjects (P=.005). At rest, both groups showed a significant arteriovenous gradient and net release of TPA antigen across the forearm (P