Oxygen modulates contractile responses to potassium and prostaglandin F2 alpha in human pial arteries.
Oxygen may modulate cerebrovascular resistance, but its direct influence on human pial arteries is unknown. We have investigated the effects of varying oxygen tension (73, 30 and 8 kPa) in depolarized (potassium) and receptor stimulated (prostaglandin F2 alpha) isolated human pial arteries. Control responses were obtained at an oxygen tension of 30 kPa. Contractions induced by prostaglandin F2 alpha and potassium showed no significant difference in potency (unaffected EC50 values) at the different oxygen concentrations. In contrast, the maximum contractions (Emax) were dependent on the oxygen tension. Potassium-induced contractions were enhanced (Emax = 107 (SE 3)% of control contractions (P less than or equal to 0.01)) at an oxygen tension of 73 kPa, whereas a reduction in tension to 8 kPa had no significant effect (97 (2)%). Prostaglandin F2 alpha-induced contractions were enhanced at 73 kPa (115 (6)%) (P = 0.02) and depressed at 8 kPa (96 (2)%) (P = 0.02). Reduction in oxygen tension induced a relaxation in depolarized and in receptor stimulated arteries, regardless of whether or not oxygen was replaced by nitrogen or by helium. Low oxygen tension relaxed arteries despite pretreatment with 2,4-dinitrophenol, an agent which blocks oxidative phosphorylation. It is concluded that a reduction in oxygen tension exerted a direct, although small, depressant effect on human pial arteries, and that this effect was not mediated exclusively by hyperpolarization or by inhibition of oxidative phosphorylation.
Reinstrup
P
P
Department of Clinical Pharmacology, University Hospital, Lund, Sweden.
Uski
T
T
Messeter
K
K
D019297:2,4-Dinitrophenol; D000328:Adult; D000368:Aged; D002536:Cerebral Arteries / Q000187:drug effects*; D004140:Dinitrophenols / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D004140:Dinitrophenols; D014475:Uncoupling Agents; D015237:Dinoprost; D019297:2,4-Dinitrophenol; D011188:Potassium; D010100:Oxygen