Medullary Thick Ascending Limb Buffer Vasoconstriction of Renal Outer-Medullary Vasa Recta in Salt-Resistant But Not Salt-Sensitive Rats

We have demonstrated previously that paracrine signaling occurs between medullary thick ascending limb (mTAL) and the contractile pericytes of outer-medullary vasa recta (VR), termed tubular-vascular cross-talk. The aim of the current study was to determine whether tubular-vascular cross-talk has a functional effect on vasoconstrictor responses to angiotensin II and to determine whether this is altered in the Dahl salt-sensitive (SS) rat. Studies were performed on salt-resistant consomic SS.13 Brown Norway (BN) and SS rats using a novel outer medullary tissue strip preparation in which freshly isolated VRs within VR bundles were perfused either alone or in combination with nearby mTAL. In VRs from SS. 13(BN) rats, angiotensin II (1 mu mol/L) increased VR bundle intracellular Ca2+ concentration 19 +/- 9 nmol/L (n=8) and reduced focal diameter in perfused VRs by -20 +/- 7% (n=5). In the presence of nearby mTAL, however, VR bundle intracellular Ca2+ concentration (-9 +/- 8 nmol/L; n=8) and VR diameter (-1 +/- 4%, n=7) in SS.13(BN) rats were unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in VR bundle intracellular Ca2+ concentration (89 +/- 48 nmol/L, n=7; 50 +/- 24%, n=8) and a reduction in VR diameter of (-17 +/- 7%, n=7; -11 +/- 4%, n=5) in both isolated VRs and VRs with nearby mTAL, respectively. In VRs with mTAL from SS13(BN) rats, inhibiton of purinergic receptors resulted in an increase in VR bundle intracellular Ca2+ concentration, indicating that purinergic signaling buffers vasoconstriction. Importantly, our in vitro data were able to predict medullary blood flow responses to angiotensin II in SS and SS.13(BN) rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13(BN) rats but not SS rats. (Hypertension. 2012; 60: 965-972.). Online Data Supplement