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Abstract
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.