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  • Title: Regulation of regional norepinephrine spillover in heart failure: the effect of angiotensin II and beta-adrenergic agonists in the forearm circulation.
    Author: Goldsmith SR, Garr M, McLaurin M.
    Journal: J Card Fail; 1998 Dec; 4(4):305-10. PubMed ID: 9924852.
    Abstract:
    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 beta-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.
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