The mechanism by which aminoglycoside antibiotics cause vasodilation of canine cerebral arteries

1 The effects of aminoglycoside antibiotics were examined in canine cerebral arteries and in cultured cerebrovascular smooth muscle cells stimulated with oxyhemoglobin (OxyHb), a blood constituent which has been implicated in the pathogenesis of cerebrovascular spasm. 2 In cerebral arterial rings precontracted with OxyHb (10 μ m ), the aminoglycosides caused a concentration‐dependent decrease in isometric tension. The EC 50 s for the relaxation were 0.46±0.1 m m ( n = 6 ), 0.53±0.08 m m ( n = 12 ), 1.6±0.3 m m ( n = 7 ) and 3.9±0.5 m m ( n = 5 ) for neomycin, gentamicin, streptomycin and kanamycin, respectively. This order of potency corresponds approximately to the number of positive charges in the molecules. 3 The aminoglycosides also inhibited the contractions to prostaglandin F 2α (1 μ m ) and depolarizing concentrations of potassium chloride (60 m m ). The order of potency was neomycin>gentamicin>streptomycin>kanamycin. 4 The relaxation was maintained in vascular preparations denuded of endothelium. 5 Neomycin (5 m m ) abolished the Ca 2+ ‐independent contraction to PGF 2α . 6 In Fura‐2‐loaded cerebrovascular smooth muscle cells, OxyHb (1 μ m ) significantly enhanced the concentration of intracellular calcium ([Ca 2+ ] i ) by 330%. The administration of neomycin, gentamicin, kanamycin and streptomycin in concentrations corresponding to the EC 50 from contractility studies, reduced the effects of OxyHb on [Ca 2+ ] i by about 50% to 221±35 n m ( n = 7 ), 270±31 n m ( n = 7 ), 229±33 n m ( n = 6 ) and 240±6 n m ( n = 5 ), respectively. 7 These results suggests that the effects of the aminoglycosides on the OxyHb‐induced contraction and the long‐term increase in [Ca 2+ ] i , may arise from several effects, including inhibition of PLC, protection of calcium extrusion mechanisms, and interference with the process of [Ca 2+ ] i accumulation.British Journal of Pharmacology (1998) 125 , 1150–1157; doi: 10.1038/sj.bjp.0702180