EVIDENCE FOR SENSING AND INTEGRATION OF BIOLOGICAL SIGNALS BY THE CAPILLARY NETWORK

The aim of this study was to explore the phenomenon first described by Dietrich (Microvasc. Res. 38: 125-135, 1989) in which a local application of norepinephrine (NE) on a capillary can temporarily reduce flow via constriction of the feeding arteriole. Our objectives were to show that this phenomenon of remote response is not limited to vasoconstriction, can be elicited by materials other than NE, shows stimulus-strength dependency, and can be integrated within the capillary network. We used an intravital micropharmacological approach to iontophoretically apply (in mM concentrations in the pipette) NE, acetylcholine (ACh), 5'-N-ethylcarboxamidoadenosine (NECA, adenosine analogue), K+, and H+ on capillaries of the frog sartorius muscle in situ. Responses were measured in terms of changes in velocity of red blood cells (V(RBC)) in capillaries or in terms of changes in arteriolar diameter. ACh (3 mM) caused significant increases in diameter (from 34 to 37 mum) and in V(RBC) (from 250 to 340 mum/s, i.e., 36%). NE (3 mM) reduced V(RBC) by 16%. The magnitude of ACh and NE velocity responses increased with increasing pipette concentration and with increasing iontophoretic current. The ACh response was blocked by a local pretreatment with atropine. NECA, K+, and H+ caused 20-40% increases in V(RBC). Dual application of NE on two capillaries fed by the same arteriole resulted in a greater V(RBC) reduction than for single NE application. Dual application of NE and ACh significantly attenuated the ACh response. We have recently shown that the remote response cannot be explained by direct diffusion from capillary to the arteriole and concluded that the capillary itself could function as a communicating medium (6). The present data suggest that, in addition to this function, capillaries may also sense and integrate biological signals.