Mechanisms underlying the antihypertensive functions of the renal medulla

Bergström, Göran; Evans, Roger G.

doi:10.1111/j.1365-201x.2004.01321.x

Cited by 37 publications

(48 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, blood supply to the medulla is more dependent on the NO vasodilatory reserve than the cortex 52. There is also substantial evidence that medullary flow, more than cortical flow, is associated with long‐term blood pressure control 53, 54. Intramedullary infusion of l ‐arginine can restore systemic hypertension in salt‐sensitive rats on a high‐salt diet, presumably by preventing reductions in medullary blood flow 55.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Emans

Janssen

Joles

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundRenal hypoxia, implicated as crucial factor in onset and progression of chronic kidney disease, may be attributed to reduced nitric oxide because nitric oxide dilates vasculature and inhibits mitochondrial oxygen consumption. We hypothesized that chronic nitric oxide synthase inhibition would induce renal hypoxia.Methods and ResultsOxygen‐sensitive electrodes, attached to telemeters, were implanted in either renal cortex (n=6) or medulla (n=7) in rats. After recovery and stabilization, baseline oxygenation (pO 2) was recorded for 1 week. To inhibit nitric oxide synthase, N‐ω‐nitro‐l‐arginine (L‐NNA; 40 mg/kg/day) was administered via drinking water for 2 weeks. A separate group (n=8), instrumented with blood pressure telemeters, followed the same protocol. L‐NNA rapidly induced hypertension (165±6 versus 108±3 mm Hg; P<0.001) and proteinuria (79±12 versus 17±2 mg/day; P<0.001). Cortical pO 2, after initially dipping, returned to baseline and then increased. Medullary pO 2 decreased progressively (up to −19±6% versus baseline; P<0.05). After 14 days of L‐NNA, amplitude of diurnal medullary pO 2 was decreased (3.7 [2.2–5.3] versus 7.9 [7.5–8.4]; P<0.01), whereas amplitudes of blood pressure and cortical pO 2 were unaltered. Terminal glomerular filtration rate (1374±74 versus 2098±122 μL/min), renal blood flow (5014±336 versus 9966±905 μL/min), and sodium reabsorption efficiency (13.0±0.8 versus 22.8±1.7 μmol/μmol) decreased (all P<0.001).ConclusionsFor the first time, we show temporal development of renal cortical and medullary oxygenation during chronic nitric oxide synthase inhibition in unrestrained conscious rats. Whereas cortical pO 2 shows transient changes, medullary pO 2 decreased progressively. Chronic L‐NNA leads to decreased renal perfusion and sodium reabsorption efficiency, resulting in progressive medullary hypoxia, suggesting that juxtamedullary nephrons are potentially vulnerable to prolonged nitric oxide depletion.

show abstract

Section: Discussionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Emans

Janssen

Joles

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…6 Given the important role of MBF in the control of sodium excretion and arterial blood pressure, 11,12,25 the renal medullary HO/CO system, by altering MBF, may be an important determinant of pressure natriuresis and thereby the long-term control of arterial blood pressure. In support of this notion, our data demonstrated that inhibition of renal medullary HO activity remarkably blunted the pressure-natriuretic response to elevations of RPP.…”

Section: Discussionmentioning

confidence: 99%

Role of Renal Medullary Heme Oxygenase in the Regulation of Pressure Natriuresis and Arterial Blood Pressure

Santos

et al. 2007

Hypertension

View full text Add to dashboard Cite

Abstract-Recent studies have demonstrated that inhibition of renal medullary heme oxygenase (HO) activity and carbon monoxide (CO) significantly decreases renal medullary blood flow and sodium excretion. Given the crucial role of renal medullary blood flow in the control of pressure natriuresis, the present study was designed to determine whether renal medullary HO activity and resulting CO production participate in the regulation of pressure natriuresis and thereby the long-term control of arterial blood pressure. In anesthetized Sprague-Dawley rats, increases in renal perfusion pressure induced significant elevations of CO concentrations in the renal medulla. Renal medullary infusion of chromium mesoporphyrin (CrMP), an inhibitor of HO activity, remarkably inhibited HO activity and the renal perfusion pressure-dependent increases in CO levels in the renal medulla and significantly blunted pressure natriuresis. In conscious Sprague-Dawley rats, continuous infusion of CrMP into the renal medulla significantly increased mean arterial pressure (129Ϯ2.5 mm Hg in CrMP group versus 118Ϯ1.6 mm Hg in vehicle group) when animals were fed a normal salt diet (1% NaCl). After rats were switched to a high-salt diet (8% NaCl) for 10 days, CrMP-treated animals exhibited further increases in mean arterial pressure compared with CrMP-treated animals that were kept on normal salt diet (152Ϯ4.1 versus 130Ϯ4.2 mm Hg). These results suggest that renal medullary HO activity plays a crucial role in the control of pressure natriuresis and arterial blood pressure and that impairment of this HO/CO-mediated antihypertensive mechanism in the renal medulla may result in the development of hypertension. Key Words: carbon monoxide Ⅲ sodium excretion Ⅲ bilirubin Ⅲ chromium mesoporphyrin Ⅲ nitric oxide Ⅲ high salt T he heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation, producing equimolar quantities of biliverdin (BV), iron, and carbon monoxide (CO). BV is subsequently converted to bilirubin (BR) by BV reductase. 1-3 It has been shown that the products of HO are involved in the regulation of cardiovascular-renal function 3 and that induction of HO-1 by pharmacological/genetic interventions improves vascular function and ameliorates both genetic and experimental forms of hypertension. [3][4][5] However, most studies showing the contribution of HO to the regulation of blood pressure are systemic interventions and focused on the vasculature. Given the crucial role of the kidneys in the long-term control of arterial blood pressure, it is imperative to determine whether local HOs in the kidneys participate in the regulation of the renal function and arterial blood pressure and how HOs and their products work to alter the blood pressure.The 2 major functional isoforms of HO are the inducible (HO-1) and the constitutive (HO-2) forms. Numerous tissues, 1 including the kidneys, 6 express HOs. Previous studies have reported that both HO-1 and HO-2 are more abundantly expressed in the renal medulla than in the renal cortex. 6,7 It...

show abstract

“…47,99 COX2 inhibition is associated with reduced renal medullary blood flow, 100 which has been shown to be associated with sodium retention and hypertension. 101 The identity of the vasodilator effect of prostanoid receptor controlling the contractile properties of the descending vasa recta that control renal medullary blood flow, remains uncertain, but EP2 and EP4 or IP receptors seem likely candidates. 69,83 The importance of EP2 and IP receptors in modulating sodium homeostasis and blood pressure is supported by studies showing that EP2 or IP receptor deficiency is associated with salt-sensitive hypertension.…”

Section: Renal Prostanoids and Blood Pressure Regulationmentioning

confidence: 99%

Physiologic and pathophysiologic roles of lipid mediators in the kidney

Hao

Breyer

2007

Kidney International

151

120

View full text Add to dashboard Cite

Small lipids such as eicosanoids exert diverse and complex functions. In addition to their role in regulating normal kidney function, these lipids also play important roles in the pathogenesis of kidney diseases. Cyclooxygenase (COX)-derived prostanoids play important role in maintaining renal function, body fluid homeostasis, and blood pressure. Renal cortical COX2-derived prostanoids, particularly (PGI2) and PGE2 play critical roles in maintaining blood pressure and renal function in volume contracted states. Renal medullary COX2-derived prostanoids appear to have antihypertensive effect in individuals challenged with a high salt diet. 5-Lipoxygenase (LO)-derived leukotrienes are involved in inflammatory glomerular injury. LO product 12-hydroxyeicosatetraenoic acid (12-HETE) is associated with pathogenesis of hypertension, and may mediate angiotensin II and TGFbeta induced mesengial cell abnormality in diabetic nephropathy. P450 hydroxylase-derived 20-HETE is a potent vasoconstrictor and is involved in the pathogenesis of hypertension. P450 epoxygenase derived epoxyeicosatrienoic acids (EETs) have vasodilator and natriuretic effect. Blockade of EET formation is associated with salt-sensitive hypertension. Ceramide has also been demonstrated to be an important signaling molecule, which is involved in pathogenesis of acute kidney injury caused by ischemia/reperfusion, and toxic insults. Those pathways should provide fruitful targets for intervention in the pharmacologic treatment of renal disease.

show abstract

Mechanisms underlying the antihypertensive functions of the renal medulla

Cited by 37 publications

References 65 publications

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Nitric Oxide Synthase Inhibition Induces Renal Medullary Hypoxia in Conscious Rats

Role of Renal Medullary Heme Oxygenase in the Regulation of Pressure Natriuresis and Arterial Blood Pressure

Physiologic and pathophysiologic roles of lipid mediators in the kidney

Contact Info

Product

Resources

About