Renal medullary interstitial infusion of diltiazem alters sodium and water excretion in rats

Lu, Shanhong; Roman, Richard J.; Mattson, David L.; Cowley, Allen W.

doi:10.1152/ajpregu.1992.263.5.r1064

Cited by 40 publications

(49 citation statements)

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“…It is surprising is that this process apparently occurs in the juxtamedullary efferent circulation that supplies the renal medulla with blood flow but not in smooth muscle of superficial efferent arterioles (13-15, 63,64). The physiological purpose of this axial heterogeneity is uncertain, but prior observations that L-channel antagonists enhance medullary blood flow seem better explained (26,37,65,169). The ability to access DVR pericytes for electrophysiological examination and measurement of intracellular Ca 2ϩ transients is a recent development (107,130,175,176).…”

Section: Discussionmentioning

confidence: 98%

Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

186

193

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Pallone, Thomas L., Zhong Zhang, and Kristie Rhinehart. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253-F266, 2003; 10.1152/ajprenal.00304.2002.-Perfusion of the renal medulla plays an important role in salt and water balance. Pericytes are smooth muscle-like cells that impart contractile function to descending vasa recta (DVR), the arteriolar segments that supply the medulla with blood flow. DVR contraction by ANG II is mediated by depolarization resulting from an increase in plasma membrane Cl Ϫ conductance that secondarily gates voltage-activated Ca 2ϩ entry. In this respect, DVR may differ from other parts of the efferent microcirculation of the kidney. Elevation of extracellular K ϩ constricts DVR to a lesser degree than ANG II or endothelin-1, implying that other events, in addition to membrane depolarization, are needed to maximize vasoconstriction. DVR endothelial cytoplasmic Ca 2ϩ is increased by bradykinin, a response that is inhibited by ANG II. ANG II inhibition of endothelial Ca 2ϩ signaling might serve to regulate the site of origin of vasodilatory paracrine agents generated in the vicinity of outer medullary vascular bundles. In the hydropenic kidney, DVR plasma equilibrates with the interstitium both by diffusion and through water efflux across aquaporin-1. That process is predicted to optimize urinary concentration by lowering blood flow to the inner medulla. To optimize urea trapping, DVR endothelia express the UT-B facilitated urea transporter. These and other features show that vasa recta have physiological mechanisms specific to their role in the renal medulla. vasa recta; perfusion; hypertension; oxygenation; urinary concentration; patch clamp; calcium; fura 2 THE MICROCIRCULATION OF THE kidney is regionally specialized. In the cortex, afferent and efferent arterioles govern the driving forces that promote glomerular filtration. A dense peritubular capillary plexus arising from efferent arterioles surrounds the proximal and distal convoluted tubules to accommodate enormous reabsorption of glomerular filtrate. In contrast, vasa recta serve needs specific to the medulla. Through the counterflow arrangement of descending (DVR) and ascending vasa recta (AVR), countercurrent exchange traps NaCl and urea deposited to the interstitium by collecting ducts and the loops of Henle. This is vital to maintain corticomedullary osmotic gradients but conflicts with the need to supply nutrient blood flow to medullary tissue. Metabolic substrates that enter the medulla in DVR blood diffuse to the AVR to be shunted back to the cortex. To deal with the threat of medullary hypoxia resulting from this process, the kidney has evolved a capacity to exert subtle control over regional perfusion of the outer and inner medulla. The details are far from clear, but much experimental evidence points to the complex interactions of many autocoids and paracrine agents to modulate vasomotor tone at various sites along the microvascular circuit. The goal of this review is to summarize ...

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Section: Discussionmentioning

confidence: 98%

Physiology of the renal medullary microcirculation

Pallone

Zhang

Rhinehart

2003

American Journal of Physiology-Renal Physiology

186

193

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“…A small cannula (0.61 mm outer diameter) was inserted 4.0 -4.5 mm into the rostral pole of the kidney to lie approximately at the corticomedullary border to facilitate the intrarenal (IR) infusion of saline (NaCl 9 g/l) or ANG (1-7) at 1 ml/h. This technique was initially shown to result in an accumulation of compound primarily in the medulla with smaller concentrations accumulating in the cortex (19). In preliminary studies, removing and sectioning the kidney at the end of the experiment verified the location of the cannula at the corticomedullary border.…”

mentioning

confidence: 87%

“…This technique has been found to deliver compounds into the renal interstitium with a distribution that is highest in the medulla but somewhat lower in the cortex (1,19). The doses used in the present study were chosen on the basis of those utilized by others (5) and scaled in a way to ensure a maximal action within the kidney with minimal spill over into the systemic circulation.…”

Section: R263 Dietary Sodium Intake and Ang (1-7)-induced Diuresis Anmentioning

confidence: 99%

Dietary sodium intake modulates renal excretory responses to intrarenal angiotensin (1–7) administration in anesthetized rats

O’Neill

Corbett

Johns

2013

American Journal of Physiology-Regulatory, Integrative and Comp

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O'Neill J, Corbett A, Johns EJ. Dietary sodium intake modulates renal excretory responses to intrarenal angiotensin (1-7) administration in anesthetized rats. Am J Physiol Regul Integr Comp Physiol 304: R260 -R266, 2013. First published December 19, 2012 doi:10.1152/ajpregu.00583.2011-Angiotensin II at the kidney regulates renal hemodynamic and excretory function, but the actions of an alternative metabolite, angiotensin (1-7), are less clear. This study investigated how manipulation of dietary sodium intake influenced the renal hemodynamic and excretory responses to intrarenal administration of angiotensin (1-7). Renal interstitial infusion of angiotensin (1-7) in anesthetized rats fed a normal salt intake had minimal effects on glomerular filtration rate but caused dose-related increases in urine flow and absolute and fractional sodium excretions ranging from 150 to 200%. In rats maintained for 2 wk on a low-sodium diet angiotensin (1-7) increased glomerular filtration rate by some 45%, but the diuretic and natriuretic responses were enhanced compared with those in rats on a normal sodium intake. By contrast, renal interstitial infusion of angiotensin (1-7) in rats maintained on a high-sodium intake had no effect on glomerular filtration rate, whereas the diuresis and natriuresis was markedly attenuated compared with those in rats fed either a normal or low-sodium diet. Plasma renin and angiotensin (1-7) were highest in the rats on the low-sodium diet and depressed in the rats on a high-sodium diet. These findings demonstrate that the renal hemodynamic and excretory responses to locally administered angiotensin (1-7) is dependent on the level of sodium intake and indirectly on the degree of activation of the renin-angiotensin system. The exact way in which angiotensin (1-7) exerts its effects may be dependent on the prevailing levels of angiotensin II and its receptor expression.angiotensin (1-7); dietary sodium; renal hemodynamics; sodium excretion THE RENIN ANGIOTENSIN SYSTEM (RAS) is a powerful endogenous hormonal cascade that plays a central role in the regulation of blood pressure, sodium balance, and body fluid homeostasis. Classically, this cascade culminates in the formation of the potent vasoconstrictor, antinatriuretic and antidiuretic peptide angiotensin II (ANG II) (7,20). ANG II is produced from angiotensin I (ANG I) primarily via angiotensin-converting enzyme (ACE) but also via the tissue enzyme chymase. The latter has been shown to contribute to the production of ANG II in the diabetic mouse kidney (21). More recently, another RAS peptide called angiotensin (1-7) [ANG (1-7)] has been described as the endogenous counter regulator of ANG II (16) via activation of its "mas" receptor (24). ANG (1-7) is formed directly from ANG II by the ACE isoform ACE 2 (27, 32) but can also be synthesized directly from ANG I via tissue-specific peptidases such as neprilysin in the kidney (2).The intrarenal actions of ANG (1-7) and its interaction with ANG II on renal hemodynamics and tubular fluid reabsorption h...

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“…A previous study from our laboratory using a radiolabeled calcium antagonist demonstrated that intramedullary infusion concentrates infused compounds in the renal medulla. 20 Interestingly, the plasma concentrations of L-ornithine and L-lysine were similarly elevated by intramedullary and intravenous infusion. Despite the similar increase in circulating L-ornithine and L-lysine, only intramedullary infusion of these amino acids decreased medullary NO and elevated MAP, suggesting that renal medullary infusion of L-ornithine and L-lysine did not elevate MAP by escape and recirculation but that locally high concentration of these amino acids decreased NO in the renal medulla to levels that resulted in systemic hypertension.…”

Section: Hypertension February 2002mentioning

confidence: 96%