Neuronal nitric oxide synthase modulates rat renal microvascular function

Abstract

This study was performed to determine the influence of neuronal nitric oxide synthase (nNOS) on renal arteriolar tone under conditions of normal, interrupted, and increased volume delivery to the macula densa segment and on the microvascular responses to angiotensin II (ANG II). Experiments were performed in vitro on afferent (21.2 ± 0.2 μm) and efferent (18.5 ± 0.2 μm) arterioles of kidneys harvested from male Sprague-Dawley rats, using the blood-perfused juxtamedullary nephron technique. Superfusion with the specific nNOS inhibitor, S-methyl-l-thiocitrulline (l-SMTC), decreased afferent and efferent arteriolar diameters, and these decreases in arteriolar diameters were prevented by interruption of distal volume delivery by papillectomy. When 10 mM acetazolamide was added to the blood perfusate to increase volume delivery to the macula densa segment, afferent arteriolar vasoconstrictor responses tol-SMTC were enhanced, but this effect was again completely prevented after papillectomy. In contrast, the arteriolar diameter responses to the nonselective NOS inhibitor, N ω-nitro-l-arginine (l-NNA) were only attenuated by papillectomy.l-SMTC (10 μM) enhanced the efferent arteriolar vasoconstrictor response to ANG II but did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II. In contrast, l-NNA (100 μM) enhanced both afferent and efferent arteriolar vasoconstrictor responses to ANG II. These results indicate that the modulating influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is dependent on distal tubular fluid flow. Furthermore, nNOS exerts a differential modulatory action on the juxtamedullary microvasculature by enhancing efferent, but not afferent, arteriolar responsiveness to ANG II.

Changes of Cell Volume and Nitric Oxide Concentration in Macula Densa Cells Caused by Changes in Luminal NaCl Concentration

“…Wilcox and Welch (34) also reported that NO in MD cells was increased in rats maintained on a high-sodium diet. The results of recent studies (11,35,36) indicate that increased distal tubular flow stimulates nNOS activity at the MD to increase NO formation. Furthermore, the regulation of local NO production may not depend only on the level of NOS activity.…”

Renal Renin-Angiotensin System

“…NO derived from nNOS counteracts afferent arteriolar constriction during enhanced TGF activity [33]. In addition, eNOS-derived NO and nNOS-derived NO respectively inhibit the afferent and efferent arteriolar responses to exogenous Ang II [34]. In Ang II-induced hypertension, the ability of nNOS-derived NO to counteract the TGF-mediated afferent arteriolar constriction is reduced [35].…”

Neuronal nitric oxide synthase, nNOS, regulates renal hemodynamics in the postnatal developing piglet

“…Experiments here utilized the selective nNOS inhibitor, l-SMTC, which allows for easy infusion into the renal artery due to its excellent water-soluble properties (40,41). l-SMTC has been used in several studies to examine the role of nNOS in renal hemodynamics including the blood-perfused juxtamedullary nephron preparation (40) and intrarenal infusion (16,42,43).…”

“…l-SMTC has been used in several studies to examine the role of nNOS in renal hemodynamics including the blood-perfused juxtamedullary nephron preparation (40) and intrarenal infusion (16,42,43). The dose of 0.027 μg/kg/min for 75 min in these experiments is based on studies that used l-SMTC intrarenal infusion (42,44).…”