Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow

Sørensen, Charlotte Mehlin; Leyssac, P. P.; Skøtt, Ole; Holstein‐Rathlou, Niels‐Henrik

doi:10.1152/ajpregu.2000.279.3.r1017

Cited by 50 publications

(60 citation statements)

References 19 publications

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“…The simplest explanation encompasses both observations. The left shift of the lower limit of autoregulation is mediated by intrarenal ANG II [29,47]. Diabetic hyperfiltration involves increased fractional proximal reabsorption resulting in increased renin secretion.…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

et al. 2012

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Aims/hypothesis In early type 1 diabetes mellitus, renal salt handling is dysregulated, so that the glomerular filtration rate becomes inversely proportional to salt intake. The salt paradox occurs in both humans and rats and, with low salt intake, results in diabetic hyperfiltration. We tested whether increased salt intake could reduce the susceptibility to injury of non-clipped kidneys in diabetic rats with pre-existing Goldblatt hypertension. Methods Male Long-Evans rats were made hypertensive and half were then made diabetic. Blood glucose was maintained at ∼20-25 mmol/l by insulin implants. One half of each received only the salt in normal chow (1% by weight) and the other half received added salt in drinking water to equal 2.7% by weight of food intake. Weekly 24 h blood pressure records were acquired by telemetry during the 4-month experiment. Results Systolic blood pressure was not affected by diabetes or increased salt intake, alone or together. Autoregulation was highly efficient in the non-clipped kidney of both intact and diabetic rats. Histological examination showed minor injury in the clipped kidney, which did not differ among groups. The non-clipped kidney showed extensive pressuredependent glomerular and vascular injury in both intact and diabetic rats. Conclusions/interpretation The relationship between pressure and injury was shifted toward lower blood pressure in diabetic rats, indicating that diabetes increased the susceptibility of the kidney to injury despite preservation of autoregulation. The increased susceptibility was not affected by high salt intake in the diabetic rats, thus disproving the hypothesis.

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Section: Discussionmentioning

confidence: 99%

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

et al. 2012

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“…31,32 In vivo micropuncture studies in rats also showed that Ang II elicits reductions in single nephron glomerular filtration rate and glomerular plasma flow and increases in both afferent and efferent arteriolar resistance. 30,[33][34][35][36] Furthermore, Ang II regulates vascular permeability through pressure-mediated mechanical injury of the endothelium and through direct nonhemodynamic effects; the latter occurs through local induction of the release of second mediators. Ang II stimulates synthesis of prostaglandins (PGs), such as PGE 2 and PGI 2 , as well as leukotriene C 4 , and thereby modulates microvascular permeability.…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

et al. 2009

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Prenatal exposure to inflammation produces offspring that are hypertensive in adulthood. This study explored alterations of the renin-angiotensin system (RAS) during the development of hypertension induced by prenatal exposure to lipopolysaccharide (LPS). In addition, the effects of an inhibitor of the nuclear transcription factor (NF)-jB (pyrrolidine dithiocarbamate, PDTC) on this process were assessed. Pregnant rats were randomly divided into four groups (n¼8): a control group, an LPS group, a PDTC group and an LPS+PDTC group. The rats in these groups were intraperitoneally administered vehicle, 0.79 mg kg À1 LPS, 100 mg kg À1 PDTC or LPS plus PDTC, respectively. LPS was given on the 8th, 10th and 12th days, whereas PDTC was given from the 8th to the 14th day during gestation. At various ages from day 1 to 25 weeks, plasma renin activity, plasma angiotensin II (Ang II) levels, renal function, glomerular number, mRNA expression levels of renal cortex renin and angiotensin-converting enzyme (ACE), the number of Ang II-positive cells and NF-jB activation were determined. The results showed that prenatal exposure to LPS resulted in significantly lower glomerular numbers and creatinine clearance rates and higher urinary protein and renal cortex ACE mRNA expression in adult offspring. Prenatal LPS also decreased the renal cortex renin mRNA expression and the number of Ang II-positive cells in offspring at 1 day of age, but these increased at 7, 16 and 25 weeks, whereas the plasma renin activity and Ang II concentration remained unchanged. Simultaneously, PDTC treatment markedly reversed the action of LPS. In conclusion, prenatal exposure to LPS resulted in alteration of the intrarenal RAS and renal damage in adult offspring rats. INTRODUCTIONThe effects of hypertension on the cardiovascular and renal systems are of major concern due to its morbidity and mortality. Though many efforts have been made to understand the pathophysiology of hypertension, it is still unclear because of its complexity. 1 A growing body of evidence indicates that hypertension is an inflammatory state wherein proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-6, contribute to the hypertensive effect. 2-5 Angiotensin II (Ang II), the major biologically active component of the reninangiotensin system (RAS), not only induces vasoconstriction, aldosterone release and sodium reabsorption by the nephron, but is also intricately interrelated with inflammation. Furthermore, the association of Ang II and inflammation induces an amplification process that involves oxidative stress and proinflammatory transcription factors, leading to progressive vascular injury 6 and having an important role in the development of hypertension and target organ damage. 2 It has been shown in our laboratory that maternal exposure to lipopolysaccharide (LPS) results in hypertension in offspring rats. 7

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“…The juxtaglomerular apparatus also participates in regulating the synthesis and release of renin, the rate-limiting enzyme for the production of AngII. This peptide is known to play an important role in resetting myogenic responses and TGF (20,24,25). During salt restriction, increased AngII enhances the sensitivity of the myogenic response (25) and shifts the TGF curve to the left, thereby preventing further loss of NaCl.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Renal Endothelial Nitric Oxide Synthase Expression by Salt Diet in Angiotensin Type-1a Receptor Gene Knockout Mice

Satô

Kihara²,

Hashimoto³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. The effects of altered dietary salt intake and/or hydralazine-induced hypotension on renal endothelial nitric oxide synthase (eNOS) expression were determined in angiotensin type-1a receptor gene knockout (At1aϪ/Ϫ) and wild-type (At1aϩ/ϩ) mice. In At1aϪ/Ϫ mice, the levels of renal cortical eNOS mRNA and protein were 5 times and 3.5 times higher, respectively, in the high-salt (4% NaCl) group than in the low-salt group (0.3% NaCl). Systemic BP of the high-salt group (105 Ϯ 4.4 mmHg) was significantly higher than that of the low-salt group (77.0 Ϯ 4.7 mmHg). When hydralazine was administered to the mutant mice fed a high-salt diet, BP was reduced to 72.5 Ϯ 1.3 mmHg, with decreases in the levels of renal eNOS mRNA and protein expression to about half of those found in nontreated group. Consistent with the results for eNOS mRNA and protein expression, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and eNOS immunoreactivity localized in the endothelium of the renal vasculature changed parallel with the amount of salt intake. In contrast to mutant mice, At1aϩ/ϩ mice did not show any changes in renal eNOS expression during the manipulation of salt intake and/or hydralazine-induced hypotension. These results suggest that At1a receptor-mediated inputs play critical roles in maintaining renal vascular eNOS expression and activity during changes in salt-water balance and systemic BP.The endothelial nitric oxide synthase (eNOS) is distributed throughout the renal vasculature, from the renal arterial branches to the glomerular capillaries. NO synthesized by eNOS in response to renal perfusion pressure and the tubuloglomerular feedback system is thought to be an important modulator of vascular tone. Renal perfusion pressure has been shown to increase urinary NO 2 /NO 3 excretion as well as output current from an electrode inserted into the renal cortex (1).eNOS is a constitutively expressed enzyme responsible for the generation of basal NO release from endothelial cells. The major stimuli of enzyme activity include shear stress and/or pressure stretch. In the kidney, however, the regulation of eNOS activity under various physiologic conditions is not well understood. Previous experiments testing the effects of altered salt intake or BP on renal eNOS activity have yielded inconsistent results (2-8).While there is little information on the endogenous factors that regulate eNOS expression within the kidney, angiotensin II

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Role of the renin-angiotensin system in regulation and autoregulation of renal blood flow

Cited by 50 publications

References 19 publications

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

Prenatal exposure to lipopolysaccharide alters the intrarenal renin–angiotensin system and renal damage in offspring rats

Alterations in Renal Endothelial Nitric Oxide Synthase Expression by Salt Diet in Angiotensin Type-1a Receptor Gene Knockout Mice

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