title: Modulation by carbon dioxide and pH of the contractile responses to potassium and prostaglandin F2 alpha in isolated human pial arteries.
abstract: Variation of PCO2 with concomitant changes in extracellular pH (pHo) may modulate cerebrovascular resistance, but the direct actions of carbon dioxide and pHo on human cerebral arteries are unknown. In this study, we have evaluated the effects of different carbon dioxide tensions (2.7, 4.2 and 7.2 kPa) with either fixed (pHo = 7.44) or concomitant changes in pHo, on contractions induced by depolarization (potassium) or receptor stimulation (prostaglandin F2 alpha) in isolated human pial arteries. Isolated changes in PCO2 had no significant effect on either potency (unchanged EC50 value) or the maximum response (Emax) in potassium-contracted arteries. Hypercapnia with uncompensated pHo significantly decreased both EC50 and Emax values, whereas uncompensated hypocapnia significantly increased the EC50 value without any effect on Emax. Concentration-response curves induced by prostaglandin (PG) F2 alpha were shifted significantly to the right (increased EC50 = decreased potency) during both hypo- and hypercapnia, independent of changes in pHo. The maximal responses were enhanced significantly during hypocapnia (Emax = 110 (SEM 2)%), but this enhancement was converted into a slight attenuation when pHo was compensated (Emax = 92 (4)%). Hypercapnia, with or without compensation of pHo, decreased the Emax values to 69 (16)% and 73 (9)%, respectively. We conclude that hypocapnia increases contractility in human pial arteries--an effect which is reversed by compensation of pHo. In contrast, the hypercapnic decrease of PGF2 alpha-induced contractions appears to be independent of pHo. The results confirm a relationship between contractility and pHo, but do not exclude a direct action of carbon dioxide in receptor-stimulated arteries.
authors: Department of Clinical Pharmacology, Neurosurgery and Anesthesiology, University Hospital, Lund, Sweden.
authors: P
authors: P
authors: Reinstrup
authors: T
authors: T
authors: Uski
authors: K
authors: K
authors: Messeter
mesh_terms: D000328:Adult; D000368:Aged; D002245:Carbon Dioxide / Q000494:pharmacology*; D002550:Cerebral Veins / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010313:Partial Pressure; D011188:Potassium / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002245:Carbon Dioxide; D015237:Dinoprost; D011188:Potassium