Effects of yohimbine, an alpha 2-adrenoceptor antagonist, on experimental neurogenic orthostatic hypotension.
Yohimbine has been proposed for the treatment of neurogenic orthostatic hypotension; however, no controlled trial has been performed in experimental models of orthostatic hypotension or in patients with autonomic failure. The aim of the present study was to compare the effects of yohimbine (0.05 mg/kg, intravenously [i.v.]) and placebo (saline) in a new model of neurogenic orthostatic hypotension obtained by sinoaortic denervation (SAD) in chloralose-anaesthetized dogs. Blood pressure, heart rate, noradrenaline plasma levels and systolic blood pressure and heart rate short-term variabilities (calculated on low frequency [40-50 MHz] and high frequency [390-490 MHz] bands) were measured in supine position and after a 10 min 80 degrees head-up tilting. The drugs were administered in a double-blind cross-over randomized fashion. The head-up tilting performed in normal animals increased diastolic blood pressure (+12 +/- 4 mmHg), heart rate (+39 +/- 12 beats per minute [bpm]), the low frequency band of systolic blood pressure and noradrenaline plasma level, without changing systolic blood pressure or heart rate variability. In SAD dogs, a marked fall in systolic (-80 +/- 11 mmHg) and diastolic (-43 +/- 4 mmHg) blood pressures was observed within 1 min after placebo, without modification in heart rate, systolic blood pressure and heart rate short-term variabilities and noradrenaline plasma levels. In SAD dogs, yohimbine (0.05 mg/kg, i.v.) delayed the blood pressure fall elicited by head-up tilting, but failed to modify its magnitude. These results show that, in the model of orthostatic hypotension obtained by SAD, yohimbine, at an alpha 2-adrenoceptor selective dose (0.05 mg/kg), delays the fall in blood pressure elicited by head-up tilting. The effect of yohimbine can be explained by an increase in sympathetic tone.
Verwaerde
P
P
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, Toulouse, France.
Tran
M A
MA
Montastruc
J L
JL
Senard
J M
JM
Portolan
G
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003714:Denervation; D004195:Disease Models, Animal; D004285:Dogs; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007024:Hypotension, Orthostatic / Q000097:blood / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D011897:Random Allocation; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism; D012850:Sinus of Valsalva / Q000294:innervation / Q000601:surgery; D015016:Yohimbine / Q000494:pharmacology / Q000627:therapeutic use*
D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D009638:Norepinephrine; D004837:Epinephrine