Effect of amlodipine on norepinephrine kinetics and baroreflex function in patients with congestive heart failure.
BACKGROUND
The use of calcium channel blocking drugs is controversial in heart failure, partly because of concerns about neurohormonal stimulation. Preliminary data suggest that the newer agent amlodipine may be useful in this syndrome. Suppression of sympathetic activity either directly or by sensitized baroreflex function could be contributing factors to the clinical use of this drug.


OBJECTIVE
To assess the effect of short-term amlodipine therapy on baseline measures of sympathetic activity and baroreflex function in patients with chronic stable congestive heart failure (CHF).


METHODS
Seven patients with chronic CHF (New York Heart Association functional class II or III, moderate to severe reduction in left ventricular systolic function) were studied. All patients underwent baroreflex testing with head-up tilt, head-down tilt, and head-down tilt with phenylephrine infusion. Heart rate, mean arterial pressure, forearm blood flow and resistance, and plasma norepinephrine (NE) kinetics were assessed at baseline and after each baroreflex perturbation on three occasions: a control test and after 10 days each of placebo and amlodipine therapy.


RESULTS
Plasma NE and NE spillover did not significantly increase after amlodipine administration compared with control and placebo tests (488 +/- 119 pg/ml vs 350 +/- 85 and 325 +/- 87 pg/ml). In three subjects, plasma NE levels were essentially unchanged, whereas in four they rose markedly (289 +/- 87 pg/ml at control vs 551 +/- 158 pg/ml). There was no difference in the response of any variable during baroreflex perturbations after amlodipine administration compared with control and placebo tests. One subject who tolerated head-down tilt coupled with phenylephrine administration during the control and placebo tests became markedly short of breath during the same intervention after amlodipine administration. Plasma NE levels in this patient had risen markedly while receiving amlodipine and were not appropriately suppressed during the baroreflex loading maneuver.


CONCLUSIONS
Short-term therapy with amlodipine does not suppress sympathetic activity or alter efferent responses to baroreflex perturbation in patients with stable chronic CHF. Significant increases in plasma NE and NE spillover and abnormal responses to baroreflex stimulation are possible after administration of this drug. The relevance of these findings to studies in larger number of patients requires further study.
Goldsmith
S R
SR
Hennepin County Medical Center and the University of Minnesota, Minneapolis 55415, USA.
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002316:Cardiotonic Agents; D002908:Chronic Disease; D004525:Efferent Pathways / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D018475:Head-Down Tilt; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D010656:Phenylephrine; D010919:Placebos; D019275:Radiopharmaceuticals; D012039:Regional Blood Flow / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced; D013566:Sympathomimetics / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D018667:Tilt-Table Test; D014316:Tritium; D014655:Vascular Resistance / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology
D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D018377:Neurotransmitter Agents; D010919:Placebos; D019275:Radiopharmaceuticals; D013566:Sympathomimetics; D014316:Tritium; D017311:Amlodipine; D010656:Phenylephrine; D009638:Norepinephrine