Presynaptic modulation of sympathetic nerve transmission--an element in vasomotor control

We have earlier presented evidence that adenosine may create vasodilation via presynaptic inhibition of sympathetic nerve fibers to muscle arterioles. In the present study the effect of selective adenosine antagonists on arteriolar diameter was investigated, using an autoperfused frog muscle (m. cutaneus pectoris). During application of the antagonists arteriolar diameter reductions were observed in the transparent, transilluminated muscle. The sulfonylated xanthine derivatives 8-(p-sulfo)phenyltheophylline (8-PS phi T), 8-(m-sulfo)phenyltheophylline (8-MS phi T) and 1,3-dipropyl-8-p-sulfonphenylxanthine (DPSPX) are all considered to be selective competitive adenosine antagonists without unspecific intracellular effects. Topical application of each of these compouns on resting muscle resulted in a dose-dependent arteriolar contraction. The constriction was immediately reversed by addition of the adrenergic alpha-receptor blocker phentolamine (7.1 x 10(-5) M), indicating that the arteriolar contraction was due to activation of postjunctional alpha-receptors present in vascular smooth muscle. Also, the A1-selective adenosine agonist (-)-N6-(R-phenylisopropyl)-adenosine (R-PIA) eliminated the arteriolar constriction. These effects suggest, that the xanthine derivatives release the sympathetic nerve terminals from inhibition by endogenous adenosine. When nerve fibers were blocked by tetrodotoxin (TTX), 3 x 10(-6)M or when the frogs had been chemically sympathectomized with 6-hydroxydopamine (6-OHDA), no significant arteriolar contraction was observed during adenosine antagonist administration, complying with the view that in resting muscle endogenous adenosine acts presynaptically to inhibit sympathetic nerve terminals. These results suggest that presynaptic adenosine effects are not only involved in regulation of frog skeletal muscle blood flow in response to activity, but also play a role in the control of arteriolar tone in resting muscle.