The afferent arteriole--the target for macula densa-generated signals.
The contractile characteristics of the afferent arteriole revealed in the present series of experiments lead one to predict that TGF-induced vasoconstriction should be dependent on both A-II and adenosine. In fact, previous evidence has suggested a role for both adenosine and angiotensin in the TGF mechanism. Acceleration of adenosine deamination as well as adenosine receptor blockade markedly reduced the effect of distal NaCl concentration on SNGFR or PSF. Conversely, inhibition of adenosine breakdown or cellular adenosine uptake, two interventions which are likely to increase interstitial adenosine levels, augmented TGF responses. The same effect was seen when adenosine1-receptor analogs were locally applied by microinfusion. The administration of A-II-converting-enzyme blockers or A-II-receptor antagonists reduced TGF responses, while peritubular or intravenous administration of A-II augmented them. Furthermore, the inhibition of TGF responses caused by volume expansion-induced reductions in plasma A-II concentrations could be restored to normal by A-II infusion. The present results raise the possibility that normal TGF responsiveness depends upon the availability of both adenosine and A-II in sufficiently high concentrations. Figure 1 outlines a mechanism of this mutual dependency. One may assume that adenosine is generated as a consequence of NaCl-dependent changes in NaCl transport by macula densa cells or by TALH cells in the immediate vicinity of the macula densa. The absence of capillaries in the juxtaglomerular interstitium could permit an accumulation of the autacoid to an extent not possible in other regions of the renal interstitium.(ABSTRACT TRUNCATED AT 250 WORDS)