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 rats, angiotensin II (1 μmol/L) increased VR bundle intracellular Ca 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 Ca concentration (-9 ± 8 nmol/L; n=8) and VR diameter (-1 ± 4%, n=7) in SS.13 rats were unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in VR bundle intracellular Ca 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 rats, inhibiton of purinergic receptors resulted in an increase in VR bundle intracellular Ca 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 rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13 rats but not SS rats.
|Original language||English (US)|
|Number of pages||8|
|State||Published - Oct 1 2012|
- blood flow regulation
- purinergic effect
ASJC Scopus subject areas
- Internal Medicine