Increased shear stress–released NO and decreased endothelial calcium in rat isolated perfused juxtamedullary nephrons

Pittner, J.; Wolgast, M.; Casellas, Daniel; Persson, A. Erik G.

doi:10.1111/j.1523-1755.2005.00073.x

Cited by 28 publications

(21 citation statements)

References 29 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…27,28 Such a mechanism may also be active to attenuate renin secretion in the juxtaglomerular cells. Interestingly, it has been shown recently that the release of NO and the cytosolic calcium concentration in endothelial cells of afferent arterioles are dependent on intravasal pressure, 29 supporting the idea that endothelial cells can function as primary mechanosensors. Moreover, a close spatial contact of renin secreting cells with endothelial cells in fact modulates renin secretion.…”

Section: Discussionmentioning

confidence: 76%

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

Wagner

Wit²,

Kurtz³

et al. 2007

Circulation Research

181

258

View full text Add to dashboard Cite

Abstract-Renin secretion and synthesis in renal juxtaglomerular cells are controlled by short feed back loops involving angiotensin II and the intrarenal blood pressure. The operating mechanisms of these negative feed back regulators are widely unknown, except for the fact that both require calcium to exert their inhibitory action. We here show that in the absence of connexin40 (Cx40), which form gap junctions between juxtaglomerular and endothelial cells, the negative control of renin secretion and synthesis by angiotensin II and by intravasal pressure is abrogated, while the regulation by salt intake and ␤-adrenergic stimulation is maintained. Renin secretion from Cx40-deficient kidneys or wild-type kidneys treated with the nonselective gap junction blocker 18␣-glycyrrhetinic acid (10 mol/L) resembles the situation in wild-type kidneys in the absence of extracellular calcium. This disturbed regulation is reflected by an enhanced plasma renin concentration despite an elevated blood pressure in Cx40-deficient mice. These findings indicate that Cx40 connexins and likely intercellular communication via Cx40-dependent gap junctions mediate the calcium-dependent inhibitor effects of angiotensin II and of intrarenal pressure on renin secretion and synthesis. Because Cx40 gap junctions are also formed between renin producing cells and endothelial cells our finding could provide additional information to suggest that the endothelium may be strongly involved in the control of the renin system. (Circ Res. 2007;100:556-563.)

show abstract

Section: Discussionmentioning

confidence: 76%

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

Wagner

Wit²,

Kurtz³

et al. 2007

Circulation Research

181

258

View full text Add to dashboard Cite

show abstract

“…NO generated by endothelial (e)NOS is triggered by two stimuli in the afferent arteriolar vasculature: shear stressdependent continuous release (19) and agonist-induced release independent of physiological stimuli (18). In experiments with perfused arterioles, application of a simple contractile stimuli that does not induce NO by itself, such as 100 mM KCl, may still alter flow and consequently shear stress, due to the reduced diameter of the vessel.…”

Section: Discussionmentioning

confidence: 99%

Losartan increases NO release in afferent arterioles during regression ofl-NAME-induced renal damage

Helle

Iversen

Chatziantoniou

2010

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Inhibition of nitric oxide synthesis (NOS) induces hypertension and heavy proteinuria. Renal structure and function have shown striking improvement after interventions targeting ANG II or endothelin (ET) receptors in rats recovering after long-term NOS inhibition. To search for mechanisms underlying losartan-assisted regression of renal disease in rodents, we measured NO release and contractility to ET in afferent arterioles (AAs) from Sprague-Dawley rats recovering for 2 wk after 4 wk of N G -nitro-L-arginine methyl ester treatment. Losartan administration during the recovery period decreased blood pressure (113 Ϯ 4 vs. 146 Ϯ 5 mmHg, P Ͻ 0.01), reduced protein/creatinine ratio more (proteinuria decrease: ⌬1,836 Ϯ 214 vs. ⌬1,024 Ϯ 180 mg/mmol, P Ͻ 0.01), and normalized microvascular hypertrophy (AA media/lumen ratio: 1.74 Ϯ 0.05 vs. 2.09 Ϯ 0.08, P Ͻ 0.05) compared with no treatment. In diaminofluorescein-FM-loaded AAs from losartan-treated animals, NO release (% of baseline) was increased compared with untreated animals after stimulation with 10 Ϫ7 M ACh (118 Ϯ 4 vs. 90 Ϯ 7%, t ϭ 560 s, P Ͻ 0.001) and 10 Ϫ9 M ET (123 Ϯ 4 vs. 101 Ϯ 5%, t ϭ 560 s, P Ͻ 0.001). There was also a blunted contractile response to 10 Ϫ7 M ET in AAs from losartan-treated animals compared with untreated animals (⌬4.01 Ϯ 2.9 vs. ⌬14.6 Ϯ 1.7 m, P Ͻ 0.01), which disappeared after acute NOS inhibition (⌬10.7 Ϯ 3.7 vs. ⌬12.5 Ϯ 2.9 m, not significant). Contractile dose responses to ET (10 Ϫ9 , 10 Ϫ8 , 10 Ϫ7 M) were enhanced by NOS inhibition and blunted by exogenous NO (10 Ϫ2 mM S-nitroso-N-acetyl-penicillamine) in losartan-treated but not in untreated vessels. Reducing blood pressure similar to losartan with hydralazine did not improve AA hypertrophy, ET-induced contractility, ET-induced NO release, and NO sensitivity. In conclusion, blockade of the local action of ANG II improved endothelial function in AAs, a mechanism that is likely to contribute to the beneficial effects of AT 1aR antagonism during the recovery of renal function after long-term NOS inhibition in rats.endothelin; nitric oxide; endothelial dysfunction; angiotensin II; vascular remodeling DETERIORATION OF RENAL FUNCTION is a result of several mechanisms, such as disturbances of renal blood flow (RBF), endothelial dysfunction, inflammation, fibrosis, or increased deposition of extracellular matrix. At present, few therapeutic tools are available to halt these processes, and the final result is often chronic renal failure. The only available treatments for these patients are dialysis or renal transplantation, costly replacement therapies that are available only for a limited portion of the world's population. An important challenge in modern medicine is therefore the development of intervention strategies that may halt or reverse the development of chronic renal failure.Drugs that are able to suppress the renin-angiotensin system have shown remarkable results in reversal of chronic renal disease in rodents (1, 3). In contrast, large-scale human trials showed less effect of AT 1a...

show abstract

“…A16. As ⌽rb increases, SNO increases (35,51). ⍀NO is calculated as a function of SNO, as shown in Eq.…”

Section: R241mentioning

confidence: 99%

“…Additionally, to develop a more inclusive model, three new mechanisms were introduced: nitric oxide (NO) (27,35,47,51), the myogenic response (10,18,21), and the effect of angiotensin II on afferent arteriolar resistance (12). Thus the work presented here is a more detailed cardiovascular model with two kidneys.…”

mentioning

confidence: 99%

A mathematical model of long-term renal sympathetic nerve activity inhibition during an increase in sodium intake

Karaaslan

Denizhan

Hester

2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

It is well known that renal nerves directly affect renal vascular resistance, tubular sodium reabsorption, and renin secretion. Inhibition of renal sympathetic nerve activity (RSNA) decreases renal vascular resistance, tubular sodium reabsorption, and renin secretion, leading to an increase in sodium excretion. Although several studies show that inhibition of RSNA promotes sodium excretion during an acute blood volume expansion, there is limited research relating to the importance of RSNA inhibition that contributes to sodium homeostasis during a long-term increase in sodium intake. Therefore, to dissect the underlying mechanisms of sodium excretion, a mathematical model of a cardiovascular system consisting of two kidneys, each with an independent RSNA, was developed. Simulations were performed to determine the responses of RSNA and sodium excretion to an increased sodium intake. In these simulations, RSNA in the left kidney was fixed at its normal steady-state value, while RSNA in the contralateral kidney was allowed to change normally in response to the increased sodium intake. The results demonstrate that the fixed-RSNA kidney excretes less sodium than the intact-RSNA collateral kidney. Because each kidney is exposed to the same arterial pressure and circulatory hormones, the impaired sodium excretion in the absence of RSNA inhibition supports the hypothesis that RSNA inhibition contributes to natriuresis in response to a long-term increase in sodium intake.

show abstract

Increased shear stress–released NO and decreased endothelial calcium in rat isolated perfused juxtamedullary nephrons

Cited by 28 publications

References 29 publications

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

Connexin40 Is Essential for the Pressure Control of Renin Synthesis and Secretion

Losartan increases NO release in afferent arterioles during regression ofl-NAME-induced renal damage

A mathematical model of long-term renal sympathetic nerve activity inhibition during an increase in sodium intake

Contact Info

Product

Resources

About