Propranolol induces acute natriuresis by β blockade and dopaminergic stimulation

1976 ◽  
Vol 54 (5) ◽  
pp. 683-691 ◽  
Author(s):  
M. C. Carrara ◽  
A. D. Baines
Keyword(s):  
Heart Rate ◽  
Sodium Excretion ◽  
Fold Increase ◽  
Nerve Function ◽  
Distal Nephron ◽  
Salt Diet ◽  
Blocking Effects ◽  
Low Salt ◽  
Dopaminergic Stimulation ◽  
Postganglionic Nerve

dl-Propranolol (0.8–1.6 mg/kg∙h for 1 h) produced a transient two- to three-fold increase in sodium excretion in nondiuretic rats infused with Pitressin and aldosterone and in water diuretic rats. Sodium excretion increased more in rats depleted of renin by chronic Doca and salt administration than in rats maintained on a low salt diet. An angiotensin inhibitor (1,sarcosine-8,valine angiotensin II) decreased sodium excretion. Therefore the natriuresis was not mediated by antidiuretic hormone, aldosterone, or renin–angiotensin. d-Propranolol did not produce a natriuresis. Prior treatment with phenoxybenzamine did not prevent the natriuretic response but chlorisondamine pretreatment did. The natriuresis is produced by β blockade and requires postganglionic nerve function but is independent of α receptors. dl-Propranolol decreased heart rate and cardiac output but systemic pressure did not fall and renal blood flow increased. This suggests a dopamine-mediated renal vasodilation and natriuresis. Haloperidol and pimozide, both dopamine blocking agents with minimal β blocking effects, prevented the natriuretic response. We conclude that propranolol may increase sodium excretion directly by blocking β receptors in the distal nephron and indirectly by dopamine-mediated renal vasodilation.

Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron

2012 ◽  
Vol 303 (9) ◽  
pp. F1289-F1299 ◽  
Author(s):  
Viatcheslav Nesterov ◽  
Anke Dahlmann ◽  
Bettina Krueger ◽  
Marko Bertog ◽  
Johannes Loffing ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Single Channel ◽  
Collecting Duct ◽  
Epithelial Sodium Channel ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Salt Diet ◽  
Low Salt ◽  
Immunohistochemical Evidence ◽  
Epithelial Sodium Channel Enac

Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na+ channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (Δ Iami) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased Δ Iami in CNT/CCD but had little effect on Δ Iami in DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS−/−) mice that lack aldosterone. In CNT/CCD of AS−/− mice, Δ Iami was lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS−/− mice, Δ Iami was similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.

scholarly journals Role of epoxyeicosatrienoic acids (EETs) in mediation of dopamine's effects in the kidney

2013 ◽  
Vol 305 (12) ◽  
pp. F1680-F1686 ◽  
Author(s):  
Ming-Zhi Zhang ◽  
Yinqiu Wang ◽  
Bing Yao ◽  
Leslie Gewin ◽  
Shouzuo Wei ◽  
...  
Keyword(s):  
Sodium Excretion ◽  
Urine Volume ◽  
Urinary Sodium Excretion ◽  
Urinary Sodium ◽  
High Salt ◽  
Epoxyeicosatrienoic Acids ◽  
Wild Type ◽  
Salt Diet ◽  
Low Salt ◽  
Renal Dopamine

We have recently demonstrated that intrarenal dopamine plays an important role in preventing the development of systemic hypertension. Similarly, renal cytochrome P-450 (CYP)-epoxygenase-derived arachidonic acid metabolites, epoxyeicosatrienoic acids (EETs), also are antihypertensive through inhibiting sodium reabsorption and vasodilation. The potential interaction between renal dopamine and epoxygenase systems was investigated. Catechol- O-methyl-transferase (COMT)−/− mice with increased intrarenal dopamine levels and proximal tubule deletion of aromatic amino acid decarboxylase (ptAADC−/−) mice with renal dopamine deficiency were treated with a low-salt diet or high-salt diet for 2 wk. Wild-type or Cyp2c44−/− mice were treated with gludopa, which selectively increased renal dopamine levels. In low salt-treated mice, urinary EET levels were related to renal dopamine levels, being highest in COMT−/− mice and lowest in ptAADC−/− mice. In high salt-treated mice, total EET and individual EET levels in both the kidney and urine were also highest in COMT−/− mice and lowest in ptAADC−/− mice. Selective increases in renal dopamine in response to gludopa administration led to marked increases in both total and all individual EET levels in the kidney without any changes in blood levels. qRT-PCR and immunoblotting indicated that gludopa increased renal Cyp2c44 mRNA and protein levels. Gludopa induced marked increases in urine volume and urinary sodium excretion in wild-type mice. In contrast, gludopa did not induce significant increases in urine volume or urinary sodium excretion in Cyp2c44−/− mice. These studies demonstrate that renal EET levels are maintained by intrarenal dopamine, and Cyp2c44-derived EETs play an important role in intrarenal dopamine-induced natriuresis and diuresis.

scholarly journals Loss of renal medullary endothelin B receptor function during salt deprivation is regulated by angiotensin II

2012 ◽  
Vol 303 (5) ◽  
pp. F659-F666 ◽  
Author(s):  
Wararat Kittikulsuth ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Receptor Binding ◽  
Sodium Excretion ◽  
Receptor Expression ◽  
Ang Ii ◽  
Receptor Function ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
Low Salt ◽  
Renal Inner Medulla ◽  
Endothelin B

We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ETB) receptor function in rats. Moreover, this was associated with a reduction of ETB receptor expression in the renal inner medulla. The aim of this present work was to investigate the effect of a physiological increase in endogenous ANG II (low-salt diet) on the renal ET system, including ETB receptor function. We hypothesized that endogenous ANG II reduces renal medullary ETB receptor function during low-salt intake. Rats were placed on a low-salt diet (0.01–0.02% NaCl) for 2 wk to allow an increase in endogenous ANG II. In rats on normal-salt chow, the stimulation of renal medullary ETB receptor by ETB receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 ± 0.4 from baseline vs. 10.5 ± 1.3 μl/min following S6c infusion; P < 0.05) and sodium excretion (0.38 ± 0.06 vs. 1.23 ± 0.17 μmol/min; P < 0.05). The low-salt diet reduced the ETB-dependent diuresis (4.5 ± 0.5 vs. 6.1 ± 0.9 μl/min) and natriuresis (0.40 ± 0.11 vs. 0.46 ± 0.12 μmol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ETB receptor function; urine flow was 7.1 ± 0.9 vs. 15.9 ± 1.7 μl/min ( P < 0.05), and sodium excretion was 0.4 ± 0.1 vs. 1.1 ± 0.1 μmol/min ( P < 0.05) before and after intramedullary S6c infusion, respectively. Receptor binding assays determined that the sodium-depleted diet resulted in a similar level of ETB receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ETB receptor binding (1,414 ± 95 vs. 862 ± 50 fmol/mg; P < 0.05). We conclude that endogenous ANG II attenuates renal medullary ETB receptor function to conserve sodium during salt deprivation independently of receptor expression.

scholarly journals Is Renal β-Adrenergic-WNK4-NCC Pathway Important in Salt Hypertension of Dahl Rats?

2019 ◽  
pp. 873-882 ◽  
Author(s):  
J. Zicha ◽  
S. Hojná ◽  
Z. Vaňourková ◽  
L. Kopkan ◽  
I. Vaněčková
Keyword(s):  
Sodium Excretion ◽  
Salt Intake ◽  
Adrenergic Stimulation ◽  
Salt Diet ◽  
Low Salt ◽  
Salt Hypertension ◽  
Propranolol Treatment ◽  
Β Blocker ◽  
Hypertension Development ◽  
Experimental Group

In 2011 Fujita and coworkers proposed that β-adrenergic stimulation causes decreased serine/threonine-protein kinase WNK4 transcription leading to the activation of Na-Cl cotransporter (NCC) which participates in salt sensitivity and salt hypertension development in rodents. The aim of our study was to investigate whether the above hypothesis is also valid for salt hypertension of Dahl rats, which are characterized by high sympathetic tone and abnormal renal sodium handling. Male 8-week-old salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats were fed either low-salt diet (LS, 0.4 % NaCl) or high-salt diet (HS, 4 % NaCl) for 6 weeks. Half of the animals on either diet were chronically treated with non-selective β-blocker propranolol (100 mg/kg/day). At the end of the experiment diuresis and sodium excretion were measured prior and after hydrochlorothiazide injection (HCTZ, 10 mg/kg i.p.). Furthermore, blood pressure (BP), heart rate (HR), sympathetic (pentolinium 5 mg/kg i.v.) and NO-dependent (L-NAME 30 mg/kg i.v.) BP components were determined. Chronic HS diet feeding increased BP through sympathoexcitation in SS/Jr but not in SR/Jr rats. Concomitant propranolol treatment did not lower BP in either experimental group. Under the conditions of low salt intake HCTZ increased diuresis, natriuresis and fractional sodium excretion in SR/Jr but not in SS/Jr rats. HS diet feeding attenuated renal response to HCT in SR/Jr rats, whereas no HCTZ effect was observed in SS/Jr rats fed HS diet. Propranolol treatment did not modify diuresis or natriuresis in any experimental group. In conclusions, our present data do not support the idea on the essential importance of renal β-adrenergic-WNK4-NCC pathway in pathogenesis and/or maintenance of salt hypertension in Dahl rats.

Renal resistance to ANF in salt-depleted rats is independent of sympathetic or ANG-aldosterone systems

1997 ◽  
Vol 272 (4) ◽  
pp. F545-F550
Author(s):  
A. T. Veress ◽  
U. Honrath ◽  
C. K. Chong ◽  
H. Sonnenberg
Keyword(s):  
Renal Perfusion ◽  
Compensatory Mechanism ◽  
Salt Diet ◽  
Low Salt ◽  
The Face ◽  
Order Of Magnitude ◽  
Salt Depletion ◽  
Natriuretic Effect ◽  
6 Hydroxydopamine ◽  
Postganglionic Nerve

Chronic salt depletion was used as a model to study the mechanism of renal resistance to the natriuretic effect of atrial natriuretic factor (ANF). Rats were pretreated with furosemide and placed on a low-salt diet (<0.008% NaCl) for 1 wk before a clearance experiment. Compared with animals on a normal salt diet (0.4% NaCl), the natriuretic reponse to ANF administration was reduced by one order of magnitude and was quantitatively trivial. To assess the influence of the sympathoadrenergic system, different groups of rats were either subjected to acute unilateral renal denervation, to chronic adrenal enucleation to reduce circulating catecholamines, or to pretreatment with 6-hydroxydopamine (OHDA) to destroy sympathetic postganglionic nerve endings. None of these treatments was able to fully or even partially restore ANF natriuresis. To determine whether an effect of angiotensin on the kidney prevented the response, the specific receptor antagonist losartan (DuP-753) was administered during the week prior to the experiment. This treatment also did not influence ANF resistance. Similarly, bilateral adrenalectomy 2 wk before the experiment did not affect the renal ANF resistance in salt-depleted rats. The depressed excretory response could not be explained on the basis of reduced renal perfusion pressure or glomerular filtration rate. We conclude that undetermined compensatory mechanism(s) ensures renal salt conservation in this model in the face of even supraphysiological levels of ANF.

High Water Intake Combined with Low Sodium Intake Abolishes the Antidiuretic Effect of Angiotensin II in Conscious Dogs

1995 ◽  
Vol 89 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Gabriele Kaczmarczyk ◽  
Willehad Boemke ◽  
Dawod Zahrei-Fard ◽  
Hermann Braun
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Water Intake ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Urine Volume ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt

1. We studied post-prandial changes in renal function in dogs adapted to either low or high sodium intake with and without concomitant post-prandial infusion of angiotensin II. Six trained dogs were exposed to diets containing either 0.5 or 14.5 mmol Na+ day−1 kg−1 body weight (low or high sodium respectively). They were studied from 20 min before to 4 h after food intake. In half of the experiments a physiological dose of angiotensin II (4 ng min−1 kg−1 body weight) was administered after food intake for four post-prandial hours. The water intake was high and equal on both diets (91 ml day−1 kg−1 body weight). 2. On a high-salt diet post-prandial sodium excretion and urine volume increased considerably above fasting values. This post-prandial increase was attenuated when angiotensin II was infused (post-prandial sodium excretion was 31% ± 3% of intake without versus 10% ± 1% with angiotensin II, post-prandial urine volume was 22% ± 2% without versus 8% ± 1% with angiotensin II, P < 0.05). Post-prandial increases in glomerular filtration rate and fractional sodium excretion were attenuated during angiotensin II infusion in dogs on a high-salt diet. 3. On a low-salt diet post-prandial sodium excretion remained low with or without angiotensin II infusion, whereas urine volume increased post-prandially, and this increase was greater when angiotensin II was administered (40% ± 3% versus 34% ± 2% of intake, P < 0.05). 4. Angiotensin II infusion increased mean arterial pressure by an average of 12 mmHg in dogs on a high-salt diet (P < 0.05) and by 7 mmHg in dogs on a low-salt diet. In dogs on a high-salt diet, right atrial pressure was on an average 3 cmH2O higher with than without angiotensin II (P < 0.05). In animals on a low salt intake post-prandial right atrial pressure decreased slightly, but remained in the range of fasting values, during angiotensin II infusion. 5. Neither plasma osmolality nor plasma sodium concentration changed in any of the four protocols. 6. We conclude that the post-prandial effects of angiotensin II in dogs on a high water intake depend on the amount of concomitant sodium intake. Angiotensin II reduces the post-prandial diuresis and natriuresis when given to sodium-loaded dogs, whereas angiotensin II does not reduce post-prandial urine flow and sodium excretion rates in dogs on a low sodium intake and may even augment water excretion in this condition.

Renal nerves and catecholamine excretion

1981 ◽  
Vol 240 (1) ◽  
pp. F75-F81 ◽  
Author(s):  
N. Morgunov ◽  
A. D. Baines
Keyword(s):  
Sodium Excretion ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Renal Nerves ◽  
High Salt Diet ◽  
Salt Diet ◽  
Catecholamine Excretion ◽  
Low Salt ◽  
Baroreceptor Stimulation ◽  
Chronic Denervation

To determine which neurotransmitters are released into urine by renal nerves, we either acutely denervated one kidney or stimulated renal nerves by activation of the baroreflex. Acute denervation increased dopamine (DA) and decreased norepinephrine (NE) excretion from the denervated kidney. In contrast, DA excretion decreased and NE excretion increased progressively from the contralateral innervated kidney. Sodium excretion related directly to DA and inversely to NE excretion. In chronic denervation experiments, baroreceptor stimulation increased NE excretion by 25% more from the innervated kidney than from its contralateral denervated mate, while DA excretion increased by 50% only from the innervated kidney. Baroreflex-stimulated NE and DA excretion from innervated kidneys was reduced by prior feeding of a low salt diet. The response was completely abolished by a high salt diet. Sodium excretion increased by the same proportion from innervated and chronically denervated kidneys following baroreceptor stimulation. In conclusion, 1) renal nerves release both NE and DA, 2) after acute unilateral denervation sodium excretion related directly with DA and inversely with NE excretion, and 3) urinary excretion of NE and DA derived from renal nerves was influenced by dietary sodium intake.

scholarly journals Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis

2009 ◽  
Vol 296 (1) ◽  
pp. F67-F77 ◽  
Author(s):  
Yu-Mi Kim ◽  
Wan-Young Kim ◽  
Hyun-Wook Lee ◽  
Jin Kim ◽  
H. Moo Kwon ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Plasma Osmolality ◽  
Urea Concentration ◽  
Urea Transporter ◽  
Osmotic Diuresis ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Protein ◽  
Low Salt ◽  
Urine Concentrating Ability

In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and tonicity-enhanced binding protein (TonEBP) transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low-protein diet (LPD) or a 0.4% low-salt diet (LSD) to decrease the total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.

scholarly journals Renal effects of the serine protease inhibitor aprotinin in healthy conscious mice

2021 ◽  
Author(s):  
Stefan Wörner ◽  
Bernhard N. Bohnert ◽  
Matthias Wörn ◽  
Mengyun Xiao ◽  
Andrea Janessa ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Serine Protease ◽  
Kidney Injury ◽  
Serine Protease Inhibitor ◽  
Tubular Function ◽  
Proteolytic Activation ◽  
Salt Diet ◽  
Low Salt ◽  
Proximal Tubular ◽  
Proximal Tubular Function

AbstractTreatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.

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