Effects of adenosine and its analogues on isolated intracerebral arterioles. Extraluminal and intraluminal application.

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Abstract
We evaluated the responses of brain parenchymal arterioles to intraluminal and extraluminal application of adenosine and its analogues. Intracerebral arterioles (28.4- to 60.3-microns diameter) were isolated from Sprague-Dawley rats, cannulated with micropipettes, and perfused in vitro. Both extraluminal and intraluminal adenosine, 5'-(N-ethylcarboxamido)adenosine (NECA), R-N6-(phenylisopropyl)adenosine (R-PIA), and S-N6-(phenylisopropyl)adenosine (S-PIA) elicited concentration-dependent dilation of these arterioles, but intraluminal application was less potent and efficacious than extraluminal application. Inosine was not vasoactive. A common order of agonist potency (NECA > adenosine > R-PIA > or = S-PIA) was determined for both extraluminal and intraluminal application. Theophylline (10 microM) caused a rightward shift of the adenosine concentration-response curve and a 50-fold reduction in potency. Intraluminal theophylline was one sixth as effective as extraluminal theophylline in antagonizing the extraluminal adenosine response, whereas intraluminal 8-sulfophenyltheophylline, a polar theophylline derivative, was ineffective. Polyadenylic acid (PolyA, 1 microM), an adenosine polymer that does not penetrate the endothelium, induced a dilation of 44.2 +/- 5.3% when applied extraluminally but had no effect when infused intraluminally. The dilator effect of PolyA was antagonized by theophylline. We conclude that: (1) intraluminal adenosine and its analogues are effective dilators of intracerebral arterioles, (2) the dilator effects of both intraluminally and extraluminally applied adenosine are predominantly mediated by A2-type receptors, and (3) adenosine receptors mediating vasodilation are not present on the luminal surface of the endothelium.