Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm

B. Clemson, L. Gaul, S. S. Gubin, D. M. Campsey, J. McConville, J. Nussberger, R. Zelis

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Abstract

To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used [3H]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 (~ 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 ~ 25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress.

Original languageEnglish (US)
Pages (from-to)684-691
Number of pages8
JournalJournal of Clinical Investigation
Volume93
Issue number2
DOIs
StatePublished - Jan 1 1994

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Angiotensin Receptors
Forearm
Angiotensin II
Norepinephrine
Lower Body Negative Pressure
Heart Failure
Nitroprusside
Diuretics
Skeletal Muscle
Exercise

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Clemson, B. ; Gaul, L. ; Gubin, S. S. ; Campsey, D. M. ; McConville, J. ; Nussberger, J. ; Zelis, R. / Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm. In: Journal of Clinical Investigation. 1994 ; Vol. 93, No. 2. pp. 684-691.
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Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm. / Clemson, B.; Gaul, L.; Gubin, S. S.; Campsey, D. M.; McConville, J.; Nussberger, J.; Zelis, R.

In: Journal of Clinical Investigation, Vol. 93, No. 2, 01.01.1994, p. 684-691.

Research output: Contribution to journalArticle

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T1 - Prejunctional angiotensin II receptors. Facilitation of norepinephrine release in the human forearm

AU - Clemson, B.

AU - Gaul, L.

AU - Gubin, S. S.

AU - Campsey, D. M.

AU - McConville, J.

AU - Nussberger, J.

AU - Zelis, R.

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N2 - To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used [3H]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 (~ 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 ~ 25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress.

AB - To determine if peripheral angiotensin II (Ang II) prejunctional receptors facilitating NE release exist in humans, we used [3H]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 (~ 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 ~ 25 pM at rest, we suggest that Ang II might facilitate NE release in severe congestive heart failure, especially under conditions of stress.

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