EFFECTS OF OXYHEMOGLOBIN ON LOCAL AND PROPAGATED VASODILATORY RESPONSES INDUCED BY ADENOSINE, ADENOSINE-DIPHOSPHATE, AND ADENOSINE-TRIPHOSPHATE IN RAT CEREBRAL ARTERIOLES

After subarachnoid hemorrhage (SAH), cerebral arteries displayed impai red vasomotor control, resulting in decreased regional cerebral blood flow. Recently, propagation of vasomotor responses has been recognized as an important regulatory mechanism in microcirculation. In this stu dy, the authors tested the hypothesis that oxyhemoglobin (OxyHb) inhib its the vasodilatory effect of chemical mediators such as adenosine an d adenine mucleotides at a local and/or propagated site. Penetrating i ntracerebral arterioles were surgically isolated from the middle cereb ral arteries of rat brains, cannulated, and observed videomicroscopica lly in an organ bath under an inverted microscope. The effects of 10(- 5) M OxyHb on vasoactive responses to adenosine, adenosine diphosphate (ADP), and adenosine triphosphate (ATP) were examined. The drugs were extraluminally applied either to the bath (10(-10)-10(-3) M) or, usin g pressure microejection (pipette concentration 10(-2) M), locally. Th e ATP and ADP initially constricted and then significantly dilated the vessels after both extraluminal application and microapplication. Fur thermore, local microstimulation by these drugs produced conducted vas odilation. Adenosine elicited significant vasodilation after both extr aluminal and local stimulation. Again, conducted vasodilation was obse rved. The vasomotor responses that were induced by a maximum local sti mulation corresponded in magnitude to those observed at bath concentra tions of 10(-5) to 10(-4) M of the same drug. Pretreatment with OxyHb constricted arterioles to an average of 87% of control and blunted ext raluminally induced dilation at low concentrations (10(-10)-10(-8)) of ATP and ADP, but did not affect vasodilation induced by 10(-4) M or g reater concentrations of ATP, ADP, or adenosine. Although the local re sponse to local microstimulation was unaltered, propagated vasodilatio n as a response to ATP, ADP, and adenosine was significantly attenuate d by OxyHb. These findings indicate that vasodilatory propagation play s an important role in the regulation of brain microcirculation and th at its impairment by OxyHb could, in part, explain the cerebral hypope rfusion that is observed after SAH.