Differential effects of increasing doses of alpha-trinositol on cerebral blood flow autoregulation.
The effect of neuropeptide Y inhibition with alpha-trinositol on the cerebral blood flow autoregulation was studied in Wistar Kyoto rats. alpha-Trinositol was tested in two doses: one dose (5 mg kg-1 hr-1) selectively affecting neuropeptide Y and one higher dose (50 mg kg-1 hr-1) affecting both neuropeptide Y and the adrenergic response. The cerebral blood flow was measured with the intracarotid 133xenon injection method in halothane nitrous oxide-anaesthetized animals. Blood pressure was raised by norepinephrine infusion and lowered by controlled haemorrhage in separate groups of rats. In addition we examined the effect of alpha-trinositol on neuropeptide Y-induced contraction of cerebral vessels in vitro. The in vitro study demonstrated inhibition of neuropeptide Y-induced contraction with a alpha-trinositol dose selective of neuropeptide Y. The in vivo study demonstrated that cerebral blood flow autoregulation was preserved after both doses of alpha-trinositol. alpha-Trinositol in the low neuropeptide Y-selective dose (5 mg kg-1 hr-1) did not affect the blood pressure limits of cerebral blood flow autoregulation, but the higher dose (50 mg kg-1 hr-1) of alpha-trinositol shifted the upper blood pressure limit of cerebral blood flow autoregulation towards lower blood pressures, an effect probably due to inhibition of both the adrenergic and neuropeptide Y systems.
Vraamark
T
T
Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Waldemar
G
G
Edvinsson
L
L
Paulson
O B
OB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009478:Neuropeptide Y / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007295:Inositol Phosphates; D009478:Neuropeptide Y; C059368:atrinositol