Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet

Purpose. To determine if the purine vasodilator adenosine participates in mediating autoregulatory dilations of the retinal microcirculation in vivo. Methods. The retinal microcirculation of isoflurane-anesthetized newborn pigs was observed by videomicroscopy (X310). Systemic hypoxia (PaO₂ = 24 ± 1 mm Hg; n = 8) or hemorrhagic hypotension (MABP = 41 ± 1 mm Hg; n = 5) was induced, and the effect of intravitreal microsuffusion of 0.4 nmol of the adenosine receptor antagonist 8-sulfophenyltheophylline (8SPT) on retinal arteriolar dilations resulting from these stimuli were measured. The effect of potentiation of endogenous interstitial adenosine concentrations with 0.2 nmol 4-nitrobenzyl-6-thioinosine (NBTI) on the response to hypotension (MABP = 43 ± 2 mm Hg; n = 4) was also determined. Results. The significant vasodilatative response of the retinal arterioles to systemic hypoxia (36 ± 8% increase in diameter above baseline; P = 0.0012) was attenuated 55% (P < 0.0001) by the adenosine antagonist 8SPT. Similarly, the significant arteriolar vasodilation induced by systemic hypotension (29 ± 3% increase in diameter; P < 0.0001) was inhibited 76% by 8SPT (P = 0.0002). When adenosine reuptake was inhibited with NBTI, the arteriolar dilation induced by hypotension (32 ± 5% increase in diameter; P = 0.0234) was potentiated 100% (P = 0.0117). Conclusions. Our finding that inhibition or potentiation of endogenous adenosine action uniquely affected retinal arteriolar dilatative responses to hypoxia and hypotension suggests that adenosine is a key participant in mediating autoregulatory adjustments in retinal blood flow in the eye of the newborn.