The local effects of systemic digoxin on the cutaneous microcirculation.
OBJECTIVE
The present study was designed to explore whether digoxin modifies cutaneous vascular responses to an endothelium-dependent vasodilator (acetylcholine) or to the vasoconstrictor norepinephrine.


METHODS
In a double-blind cross-over study 12 healthy subjects received digoxin 0.25 mg twice daily (after adequate loading doses) or placebo for a total of 11 days. Dose-response curves to iontophoresis of acetylcholine or norepinephrine were constructed at day 11. Laser Doppler flux (LDF) was measured at the same sites. Mean arterial pressure (MAP) was measured non-invasively and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP).


RESULTS
Serum concentrations of digoxin were within the therapeutic range [1.3 (0.5) ng x ml(-1); mean with (SD)]. Blood pressure and heart rate were significantly lower during supine rest under digoxin treatment [mean with (SD); minute 10 to 70 of supine rest; systolic blood pressure: 121 (11) mmHg (placebo) vs 116 (11) mmHg (digoxin); P = 0.001; diastolic blood pressure: 63 (6) mmHg vs 58 (8) mmHg; P = 0.007; heart rate: 60 (10) beats x min(-1) vs 54 (8) beats x min(-1); P = 0.001]. Digoxin also caused significantly higher baseline CVC [169 (25) Perfusion Units (PU) x mmHg(-1) (digoxin) vs 109 (14) PU x mmHg(-1)(placebo); P = 0.013] and significantly increased the vasoconstriction to norepinephrine iontophoresis. Acetylcholine iontophoresis was unaltered by digoxin treatment.


CONCLUSIONS
Digoxin does not modify the cutaneous vascular response to an administered endothelium-dependent vasodilator. It reduces resting heart rate, blood pressure and baseline cutaneous blood flow and augments the vasoconstrictive effect of exogenous norepinephrine. The findings do not support the hypothesis that digoxin lowers diastolic blood pressure through a direct action on blood vessels.
Grossmann
M
M
Department of Pharmacology, University of Texas Health Science Center, San Antonio, USA. mgrossma@rcs.urz.tu-dresden.de
Jamieson
M J
MJ
Kirch
W
W
D000109:Acetylcholine / Q000009:adverse effects / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004077:Digoxin / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000009:adverse effects / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004077:Digoxin; D000109:Acetylcholine; D009638:Norepinephrine