Differential effects of the adenosine A1 receptor agonist adenosine amine congener on renal, femoral and carotid vascular conductance in preterm fetal sheep.
1. Adenosine A(1) receptor activation is critical for endogenous neuroprotection from hypoxia-ischaemia, raising the possibility that treatment with A(1) receptor agonists may be an effective physiological protection strategy for vulnerable preterm infants. However, the A(1) receptor can mediate unwanted systemic effects, including vasoconstriction of the afferent glomerular arteriole. There is limited information on whether this occurs at doses that improve cerebral perfusion in the immature brain. 2. Therefore, in the present study, we examined whether infusion of the selective A(1) receptor agonist adenosine amine congener (ADAC) is associated with reduced renal perfusion in chronically instrumented preterm (0.7 gestation) fetal sheep. In the present study, ADAC was given in successive doses of 2.5, 5.0 and 15.0 microg, 45 min apart. 3. Treatment with ADAC was associated with a marked reduction in renal vascular conductance (and blood flow), whereas carotid conductance was increased and there was no significant effect on femoral conductance. In contrast with the stable effects of increasing ADAC dose on vascular conductance, there was a significant dose-related fall in fetal heart rate and blood pressure. 4. In conclusion, these short-term data support the concern that A(1) receptor agonist infusion can selectively impair renal perfusion, even at low doses.
Booth
Lindsea C
LC
Department of Physiology, The University of Auckland, Auckland, New Zealand.
Tummers
Leonie
L
Jensen
Ellen C
EC
Barrett
Carolyn J
CJ
Malpas
Simon C
SC
Gunn
Alistair J
AJ
Bennet
Laura
L
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D005333:Fetus / Q000098:blood supply* / Q000187:drug effects*; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D034561:Sheep, Domestic
C106045:adenosine amine congener; D000241:Adenosine