Background: Prejunctional receptors for angiotensin II (A-II) and norepinephrine (NE) have been reported to facilitate NE release. If operative in patients with congestive heart failure (CHF), such receptors could participate in positive feedback cycles amplifying sympathoactivation. Methods and Results: A-II and isoproterenol (ISO) would increase regional NE spillover via facilitation of presynaptic release of NE in the forearm circulation of patients with chronic stable CHF. A-II, ISO, and nitroprusside (NP) were sequentially infused into the brachial arteries of 10 patients with chronic stable CHF, which was attributed to dilated cardiomyopathy. Forearm blood flow (FBF) was measured via plethysmography and regional spillover of NE was measured by using the isotope dilution method of Esler. A-II (5 ng/min) produced a nonsignificant decline in FBF (1.87 ± 0.14 to 1.46 ± 0.1 mL/100 g/min, P = .07) and did not change regional NE spillover (418 ± 128 to 409 ± 121 ng/min). ISO increased FBF from 1.6 ± 0.12 to 4.3 ± 0.7 mg/100 g/min (P < .001). Regional NE spillover increased from 337 ± 86 to 856 ± 300 ng/min (P < .001). Venous NE and regional extraction of NE did not change. NP increased FBF from 2.0 ± 0.3 to 6.3 ± 1.2 mL/100 g/min (P < .001; P = NS v change with ISO) and also increased regional NE spillover (301 ± 99 to 712 ± 288 ng/min, P < .001; P = NS v change with ISO). As with ISO, venous NE and extraction of NE were not altered. Conclusions: Mild vasoconstrictor infusions of A-II do not increase regional NE spillover in the forearm circulation of patients with CHF. The β-adrenergic agonist ISO does increase regional spillover, but the effect seems to be primarily related to flow rather than presynaptic stimulation of NE release. These data argue against an important positive feedback loop involving A-II and NE on sympathoactivation, at least with the dosages of the agonists studied and in the limb circulation in chronic stable CHF.
Bibliographical noteFunding Information:
Supported by Program Project Grant HL-32427 from the National Heart, Lung, and Blood Institute. Manuscript received February 16, 1998; revised manuscriptr eceived July 22, 1998; revised manuscript accepted September 1, 1998. Reprint requests: Steven R. Goldsmith, MD, HennepinC ounty Medical Center, Cardiology Division, 701 Park Avenue, Minneapolis,M N 55415. Copyright © 1998 by Churchill Livingstone ® 1071-9164/98/0404-000658.00/0 Increased activity of the sympathetic nervous system almost certainly contributes to the progression of heart failure syndrome in patients with left ventricular dysfunction (1). The explanation for chronic sympathoacti-vation in heart failure remains elusive. More than one mechanism probably contributes. Much speculation has focused on the possible role of malfunctioning barore-flexes leading to increased central sympathetic drive, but cause-and-effect studies are lacking. Likewise, although
- Angiotensin II
- Heart failure