Mechanisms of dexmedetomidine-induced cerebrovascular effects in canine in vivo experiments.
Dexmedetomidine decreases cerebral blood flow without significantly affecting cerebral oxygen consumption in anesthetized dogs. To assess the direct cerebrovascular effects of dexmedetomidine, we investigated the responses of vasomotor tone to topical application of dexmedetomidine to pial vessels in vivo, using a parietal cranial window. Forty-one dogs were anesthetized with pentobarbital. In 20 dogs, we topically applied six concentrations of dexmedetomidine solution (10(-8), 10(-7), 10(-6), 10(-5), 10(-4), 10(-3) M) and directly measured pial arterial and venous diameters. In 10 dogs, the inhibitory effects of pretreatment of pial vessels with 10(-5) M yohimbine were examined after the application of 10(-5) dexmedetomidine. In the remaining 11 dogs, the effects of 10(-3) M dexmedetomidine were evaluated in the presence of N omega-nitro-L-arginine methyl ester (L-NAME), glibenclamide, or propranolol. Dexmedetomidine significantly constricted pial arteries and veins in a concentration-dependent manner (10(-7) M to 10(-4) M; P < 0.05). Yohimbine blocked dexmedetomidine-induced constriction of pial vessels (both large and small arteries and large veins P < 0.0001; small veins P < 0.005). However, when the highest concentration of dexmedetomidine (10(-3) M) was administered under the window, pial vessel diameter was not significantly altered. In the presence of glibenclamide, 10(-7) and 10(-3) M dexmedetomidine induced a significant decrease in pial arterial diameter compared with 10(-7) and 10(-3) M dexmedetomidine solution alone, respectively (P < 0.05). L-NAME or propranolol did not affect the dexmedetomidine-induced constriction.(ABSTRACT TRUNCATED AT 250 WORDS)
D000287:Administration, Topical; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D007093:Imidazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020926:Medetomidine; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D010841:Pia Mater / Q000098:blood supply; D011433:Propranolol / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015016:Yohimbine; D001120:Arginine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D020926:Medetomidine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester