Calcium channel modulation of alpha 1- and alpha 2-adrenergic pressor responses in conscious and anesthetized dogs.
The influence of halothane and isoflurane on alpha-adrenergic-mediated vasoconstriction before and following calcium channel modulation was investigated in chronically instrumented dogs. After ganglionic, cholinergic, and beta-adrenergic blockade, systemic hemodynamic responses following equieffective pressor doses of phenylephrine (0.6 micrograms/kg iv), a selective alpha 1 agonist, and azepexole [B-HT 933] (20 micrograms/kg iv), a selective alpha 2 agonist, were obtained. The calcium channel stimulator Bay k 8644 (0.5 and 1 micrograms.kg-1.min-1) was infused intravenously for 10 min and phenylephrine and azepexole administered at the end of each infusion. On different days, each dog was subsequently anesthetized with equihypotensive concentrations of halothane (1.7%) or isoflurane (2%) in oxygen and the same pharmacologic interventions were repeated in the presence of halothane or isoflurane. Twenty-one experiments (three groups) using seven chronically instrumented dogs were completed. Halothane and isoflurane produced significant (P less than 0.05) attenuation of the increase in arterial pressure after bolus administration of phenylephrine and azepexole. Bay k 8644 augmented the pressor responses mediated by both phenylephrine and azepexole in all three groups. Thus, halothane and isoflurane nonselectively reduced the pressor response to both alpha 1- and alpha 2-adrenergic receptor stimulation and this was probably not mediated by inhibition of transmembrane calcium flux through dihydropyridine sensitive channels.
Kenny
D
D
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226.
Pelc
L R
LR
Brooks
H L
HL
Kampine
J P
JP
Schmeling
W T
WT
Warltier
D C
DC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006221:Halothane; D007530:Isoflurane; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D002120:Calcium Channel Agonists; D010656:Phenylephrine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007530:Isoflurane; C015603:azepexole; D006221:Halothane