PREJUNCTIONAL ANGIOTENSIN-II RECEPTORS - FACILITATION OF NOREPINEPHRINE RELEASE IN THE HUMAN FOREARM

To determine if peripheral angiotensin II (Ang II) prejunctional recep tors facilitating NE release exist in humans, we used [H-3] NE kinetic methodology to measure forearm NE spillover during intrabrachial arte rial Ang II infusions in eight normal male subjects. We used the follo wing protocol to optimize conditions for demonstrating these receptors : (a) lower body negative pressure (-15 mmHg) to increase sympathetic nerve activity to skeletal muscle; and (b) intraarterial nitroprusside to maintain a high constant forearm blood flow (similar to 10 ml/min . 100 ml) to maximize the proportion of neuronally released NE that sp ills over into the circulation. During lower body negative pressure, t he following were infused intraarterially for three consecutive 20-min periods: saline, Ang II (4 ng/min), and Ang II (16 ng/min). During th e Ang II infusions, forearm venous NE increased significantly from 173 to 189 and 224 pg/ml (P < 0.01), and forearm NE spillover increased f rom 384 to 439 and 560 ng/min 100 ml (P < 0.05 for high Ang II). Forea rm NE clearance was unchanged. During low and high dose Ang II, the pl asma venous Ang II concentrations were 25 and 97 pM, respectively. Sin ce normal subjects increase plasma Ang II from 4 to 20-22 pM with exer cise, standing, or diuretic administration, and patients with severe c ongestive heart failure can have a plasma Ang II of similar to 25 pM, at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress.