Relationship between the overflow of endogenous and radiolabelled noradrenaline from canine blood perfused gracilis muscle.

Abstract

The effects of sympathetic nerve stimulation (SNS) on the overflow of endogenous noradrenaline (NA) and on vasoconstrictor responses were studied in blood perfused canine gracilis muscle in situ. A conventional tracer technique with 3H-labelled NA (3H-NA) was used in parallel. At rest there was a net extraction of endogenous NA and adrenaline across the tissue. The SNS evoked overflow of endogenous NA was frequency-dependent and logarithmically correlated to the vasoconstrictor responses. The neuronal uptake inhibitor desipramine doubled the SNS induced overflow of endogenous NA without enhancing the vasoconstrictor responses. A further fourfold increase in NA overflow was caused by a dose of the alpha-blocker phenoxybenzamine which reduced the vasoconstrictor responses by 50-75%. Less than 10% of the spontaneous 3H efflux was recovered as unmetabolized 3H-NA, whereas virtually all 3H overflow evoked by SNS was 3H-NA. The fractional release of NA or 3H-NA per nerve impulse increased with increasing frequencies of SNS under all conditions studied. Although there was a preferential release of the newly stored radiolabelled transmitter, results concerning endogenous NA and 3H-NA overflow were qualitatively similar, also under conditions with marked changes in transmitter overflow. Endogenous NA gave a more reproducible index of transmitter overflow than did 3H-NA and, in particular, total 3H. The overflow of endogenous NA closely reflects SNS evoked neuronal release of NA in blood perfused skeletal muscle and seems more suitable than conventional radiotracer techniques for studies of NA release under in vivo conditions.