Effects of octreotide on experimental neurogenic orthostatic hypotension in anaesthetized dogs.
This paper investigates the effects of octreotide (0.1 mg/kg, subcutaneous) on cardiovascular adaptation during head-up tilt test in an experimental model of neurogenic orthostatic hypotension (OH) obtained by chronic sinoaortic denervation in anaesthetized dogs. Blood pressure (BP), heart rate (HR), spectral variability (Fast Fourier transformation on 512 consecutive points, delta t: 2 Hz) and plasma catecholamine levels were measured in a double blind cross-over randomized study versus placebo, in supine position and during a head-up tilt test (80 degrees, 10 min) in six sinoaortic denervated and six control (normal) dogs. In normal dogs, head-up tilt test significantly increased HR and diastolic blood pressure (DBP). Plasma noradrenaline levels and energy of the low frequency band (40-150 mHz) of systolic blood pressure (SBP) significantly increased whereas the energy of the low frequency band of HR significantly decreased. Placebo and octreotide failed to modify supine and head-up tilt values of the measured parameters (except the value of low frequency band of SBP, which increased after octreotide). In sinoaortic denervated dogs, supine values of BP, HR and plasma noradrenaline levels were significantly higher than in controls whereas the energy of the low frequency spectral band of HR and SBP was similar to controls. Head-up tilt test induced a dramatic decrease in BP. HR, plasma noradrenaline levels and energy of the low frequency band of SBP and HR remained unchanged during head-up tilt tests. Neither supine nor head-up tilt values of these parameters were modified 45 min after octreotide or placebo administration. These results show that sinoaortic denervation is a reproducible model of OH characterized by a lack of activation of sympathetic efferent pathways during head-up tilt tests. Octreotide at the dose used remains ineffective to prevent the fall in BP under these experimental conditions.
Bordet
R
R
Service de Pharmacologie Hospitalière, Centre Hospitalier Universitaire de Lille, France.
Verwaerde
P
P
Tran
M A
MA
Marques
M A
MA
Montastruc
J L
JL
Senard
J M
JM
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000097:blood; D003714:Denervation; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007024:Hypotension, Orthostatic / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D015282:Octreotide / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000294:innervation; D016683:Supine Position; D018667:Tilt-Table Test
D002395:Catecholamines; D007328:Insulin; D015282:Octreotide