The Effect of Topical Microapplication of Norepinephrine and Benzoxathian on Cerebral Pial Arteries in Rabbit

ABSTRACT

The effects of norepinephrine and benzoxathian on the diameters of cerebral pial vessels in rabbits were studied by topical microapplication of the drugs to the perivascular environment. Vascular diameters were determined with the micrometer eyepiece on operating microscope through the craniectomized area. Physiological parameters(PaO2, PaCO2, blood pH, and systolic blood pressure) had not significantly changed during all the experiments. The observations were as follows: 1) Application of norepinephrine over the range of 5x10(-8)M to 5x10(-3)M to the cerebral pial arteries resulted in significant constriction of the vessels, with the exception of 5x10(-8)M. The dose-response curve showed a maximal constriction of 31.5+/-3.8% at 5x10(-3)M. 2) Benzoxathian produced vasodilatation at dosages over 5x10(-4)M. But there was little change of vascular diameter between dosages of 5x10(-8)M to 5x10(-5)M. The dose-response curve showed a maximal vasodilatation of 26.31+/-5.1% at 5x10(-3)M. 3) The vasoconstriction due to microapplication of norepinephrine was prevented by the inclusion of an equimolar concentration of the alpha-1 receptor antagonist, benzoxathian. 4) The vasoconstriction induced by norepinephrine occurred in higher concentration of norepinephrine than that of benzoxathian, and the vasoconstriction was proportional to the concentration of norepinephrine. 5) The pattern of responses of the pial veins corresponded with that of pial arteries. But the amplitudes of the change in the diameters of veins were less than those of the arteries. The results indicate that alpha-adrenergic receptor is present in the smooth muscles of cerebral pial arteries and veins for the sympathetic control of blood flow to the brain, and newly introduced benzoxathian acts as a highly selective alpha-1 receptor antagonist.