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 display impaired 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 study, the authors tested the hypothesis that oxyhemoglobin (OxyHb) inhibits the vasodilatory effect of chemical mediators such as adenosine and adenine nucleotides at a local and/or propagated site. Penetrating intracerebral arterioles were surgically isolated from the middle cerebral arteries of rat brains, cannulated, and observed videomicroscopically 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, using pressure microejection (pipette concentration 10(-2) M), locally. The ATP and ADP initially constricted and then significantly dilated the vessels after both extraluminal application and microapplication. Furthermore, local microstimulation by these drugs produced conducted vasodilation. Adenosine elicited significant vasodilation after both extraluminal and local stimulation. Again, conducted vasodilation was observed. The vasomotor responses that were induced by a maximum local stimulation corresponded in magnitude to those observed at bath concentrations 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 extraluminally induced dilation at low concentrations (10(-10)-10(-8)) of ATP and ADP, but did not affect vasodilation induced by 10(-4) M or greater concentrations of ATP, ADP, or adenosine. Although the local response to local microstimulation was unaltered, propagated vasodilation as a response to ATP, ADP, and adenosine was significantly attenuated by OxyHb. These findings indicate that vasodilatory propagation plays an important role in the regulation of brain microcirculation and that its impairment by OxyHb could, in part, explain the cerebral hypoperfusion that is observed after SAH.
Kajita
Y
Y
Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri, USA.
Dietrich
H H
HH
Dacey
R G
RG
D000241:Adenosine / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010108:Oxyhemoglobins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D010108:Oxyhemoglobins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine