Regional sympathetic effects of low-dose clonidine in heart failure.
This study examined the effects of low doses of intravenous clonidine on regional and global sympathetic nervous system activity in heart failure. In heart failure, adrenoceptor-blocking treatments have a limited sphere of activity. Centrally acting sympatholytic therapies should be further investigated, with a specific emphasis on targeting cardiac and renal sympathetic overactivity. In 10 patients with moderate-severe congestive heart failure, we examined the effect of intravenous clonidine on systemic, cardiac, and renal sympathetic activity and on brain monoamine turnover using the norepinephrine spillover method. In addition, we assessed the effect of clonidine on cardiac release of the sympathetic cotransmitter neuropeptide Y. A dose of 1 microg/kg of clonidine resulted in a fall in cardiac (326+/-73 to 160+/-40 pmol/min, P<0.001), renal (2.5+/-0.6 to 1.5+/-0.3 nmol/min, P=0.01), and global norepinephrine spillover (4.0+/-0.6 to 3.1+/-0.5 nmol/min, P<0.01), with a significantly disproportionate reduction in cardiac versus total-body sympathetic activity (P<0.05). No significant changes in cardiac neuropeptide Y release or in central monoamine turnover were demonstrated. Clonidine, at modest doses, significantly attenuates cardiac and renal sympathetic tone in heart failure. In addition to the beneficial effects of antiadrenergic therapy in the heart, the renal sympatholytic effect may counter the salt and water retention that is a hallmark of the condition.
Aggarwal
Anuradha
A
Baker Medical Research Institute, University of Melbourne, Melbourne, Victoria, Australia.
Esler
Murray D
MD
Morris
Margaret J
MJ
Lambert
Gavin
G
Kaye
David M
DM
D000368:Aged; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000294:innervation; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000294:innervation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009928:Organ Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013565:Sympatholytics / Q000008:administration & dosage / Q000494:pharmacology*
D009478:Neuropeptide Y; D013565:Sympatholytics; D003000:Clonidine; D009638:Norepinephrine