MEDULLARY THICK ASCENDING LIMB BUFFER VASOCONSTRICTION OF RENAL OUTER-MEDULLARY VASA RECTA IN SALT-RESISTANT BUT NOT SALT-SENSITIVE RATS

摘要

We have previously demonstrated 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^BN and SS rats using a novel outer medullary tissue strip preparation in which freshly isolated VR within VR bundles were perfused either alone or in combination with nearby mTAL. In VR from SS.13^BN rats, angiotensin II (1μM) increased VR bundle intracellular Ca²⁺ concentration ([Ca²⁺]VR) 19±9nM (n=8) and reduced focal diameter in perfused VR by (−20±7%;n=5). In the presence of nearby mTAL however, [Ca²⁺]VR (−9±8nM; n=8) and VR diameter (−1±4%, n=7) in SS.13^BN rats was unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in [Ca²⁺]VR (89±48 n=7;50±24% n=8) and a reduction in VR diameter of (−17±7;n=7 and −11±4%;n=5) in both isolated VR and VR with nearby mTAL, respectively. In VR with mTAL from SS13^BN rats, inhibiton of purinergic receptors resulted in an increase in [Ca²⁺]VR, indicating 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.