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

被引:69
作者
CLEMSON, B
GAUL, L
GUBIN, SS
CAMPSEY, DM
MCCONVILLE, J
NUSSBERGER, J
ZELIS, R
机构
[1] PENN STATE UNIV, COLL MED, DEPT MED, DIV CARDIOL, HERSHEY, PA 17033 USA
[2] PENN STATE UNIV, COLL MED, DEPT CELLULAR & MOLEC PHYSIOL, HERSHEY, PA 17033 USA
[3] UNIV HOSP LAUSANNE, DIV HYPERTENS, CH-1011 LAUSANNE, SWITZERLAND
关键词
CONGESTIVE HEART FAILURE; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; H-3] NOREPINEPHRINE KINETICS; NOREPINEPHRINE SPILLOVER;
D O I
10.1172/JCI117021
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used [H-3] NE kinetic methodology to measure forearm NE spillover during intrabrachial arterial Ang II infusions in eight normal male subjects. We used the following 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 spills over into the circulation. During lower body negative pressure, the following were infused intraarterially for three consecutive 20-min periods: saline, Ang II (4 ng/min), and Ang II (16 ng/min). During the Ang II infusions, forearm venous NE increased significantly from 173 to 189 and 224 pg/ml (P < 0.01), and forearm NE spillover increased from 384 to 439 and 560 ng/min 100 ml (P < 0.05 for high Ang II). Forearm NE clearance was unchanged. During low and high dose Ang II, the plasma venous Ang II concentrations were 25 and 97 pM, respectively. Since normal subjects increase plasma Ang II from 4 to 20-22 pM with exercise, standing, or diuretic administration, and patients with severe congestive 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.
引用
收藏
页码:684 / 691
页数:8
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