Renal Accumulation of Circulating Angiotensin II in Angiotensin II–Infused Rats

Zou, Long; Hymel, Anka; Imig, John D.; Navar, L. Gabriel

doi:10.1161/01.hyp.27.3.658

Cited by 100 publications

(127 citation statements)

References 20 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…As expected from previous studies, Val5-ANG II elicited the slowly developing hypertension previously seen with 11e5-ANG II. Furthermore, the increases in total intrarenal ANG II were similar to those found in previous studies (62). By using this experimental design, we determined how much of the ANG II came from the minipump and how much of the ANG II was formed endogenously.…”

Section: Infusions Of Va15 Ang IIsupporting

confidence: 75%

“…To evaluate mechanisms responsible for the augmented intrarenal ANG II in renin depleted kidneys, further experiments were performed using a model of ANG II infused hypertension that leads to marked suppression of both circulating and tissue renin activity (42,52,62,63). Instead of renal arterial stenosis, an osmotic minipump containing ANG II was implanted.…”

Section: Ang II Infused Hypertensionmentioning

confidence: 99%

See 1 more Smart Citation

Intrarenal Angiotensin II Augmentation in Angiotensin II Dependent Hypertension.

Navar

Harrison‐Bernard

2000

Hypertens Res

Self Cite

View full text Add to dashboard Cite

In several models of angiotensin II (ANG II) dependent hypertension, intrarenal ANG II levels increase to a much greater extent than the circulating levels even though the renal renin levels are decreased. The 2-kidney-l-clip (2K1C) Goldblatt rat model is particularly intriguing because hypertension develops in the presence of an intact kidney which would be expected to maintain sodium balance and protect against hypertension.Although the non-clipped kidney becomes renin depleted, it exhibits enhanced microvascular reactivity and increased tubular fractional sodium reabsorption. content was due to accumulation of circulating ANG II in addition to continued production of endogenous ANG II. The renal accumulation of Va15-ANG II was markedly reduced by concomitant treatment with the AT, receptor blocker, losartan. In addition, we found an unchanged overall ANG II-AT, receptor protein which probably contributes to the maintained ANG II dependent influences. Collectively, the data support the concept that there is internalization of ANG II through an AT, receptor mediated process and that some of the internalized ANG II is protected from degradation. The augmented intrarenal ANG II coupled with sustained levels of AT, receptors contribute to the continued ANG II dependent suppression of renal function and sodium excretion thereby maintaining the hypertension. (Hypertens Res 2000; 23: 291-301)

show abstract

Section: Infusions Of Va15 Ang IIsupporting

confidence: 75%

Section: Ang II Infused Hypertensionmentioning

confidence: 99%

Intrarenal Angiotensin II Augmentation in Angiotensin II Dependent Hypertension.

Navar

Harrison‐Bernard

2000

Hypertens Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…[18][19][20][21]24,26,28,29 However, little information is available regarding the prevailing kidney tissue Ang II levels in Cyp1a1-Ren2 rats following induction of either slowly developing or malignant hypertension. In the present study, I3C dosedependently increased PRA and plasma Ang II levels (see Figures 7 and 8).…”

Section: Discussionmentioning

confidence: 99%

“…In essence, I3C-controlled expression of the Cyp1a1-Ren2 transgene can be considered to be the genetic equivalent of minipump infusion of different fixed amounts of renin that are not subject to homeostatic regulation. Thus, in contrast to the Ang II-infused hypertensive rat model, in which the kidneys of Ang II-infused rats are exposed to elevated circulating Ang II levels but exhibit markedly suppressed plasma renin levels and decreased kidney renin contents, [18][19][20][21] the kidneys of hypertensive Cyp1a1-Ren2 rats are exposed to elevated circulating levels of both renin and Ang II consequent to induction of extrarenal induction of the Cyp1a1-Ren2 transgene. Accordingly, the Cyp1a1-Ren2 transgenic rat can be viewed as a high circulating renin and Ang II hypertensive model in which the elevated blood pressure (BP) is due to increased activity of the circulating or of the extrarenal tissue RAS.…”

Section: O P Y R I G H T J R a A S L I M I T E D R E P R O D U C T mentioning

confidence: 99%

“…PRA and Ang II concentrations in plasma and whole kidney tissue were determined by radioimmunoassay as extensively described and validated previously. [18][19][20][21]24,[26][27][28][29][30] Urine volume was determined gravimetrically. Inulin and PAH concentrations in both urine and plasma were measured by standard spectrophotometry.…”

Section: Journal Of the Reninangiotensinaldosterone Systemmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Clamping of Renin Gene Expression Induces Hypertension and Elevation of Intrarenal Ang II Levels of Graded Severity in Cyp1a1-Ren2 Transgenic Rats

Mitchell

Bagatell

Miller

et al. 2006

J Renin Angiotensin Aldosterone Syst

153

View full text Add to dashboard Cite

Introduction. Transgenic rats with inducible angiotensin II (Ang II)-dependent hypertension (strain name: TGR[Cyp1a1-Ren2]) were generated by inserting the mouse Ren2 renin gene, fused to the cytochrome P450 1a1 (Cyp1a1) promoter, into the genome of the rat. The present study was performed to characterise the changes in plasma and kidney tissue Ang II levels and in renal haemodynamic function in Cyp1a1-Ren2 rats following induction of either slowly developing or malignant hypertension in these transgenic rats. Materials and Methods. Arterial blood pressure (BP) and renal haemodynamics and excretory function were measured in pentobarbital sodium-anaesthetised Cyp1a1-Ren2 rats fed a normal diet containing either a low dose (0.15%, w/w for 14-15 days) or high dose (0.3%, w/w for 11-12 days) of the aryl hydrocarbon indole-3-carbinol (I3C) to induce slowly developing and malignant hypertension, respectively. In parallel experiments, arterial blood samples and kidneys were harvested for measurement of Ang II levels by radioimmunoassay. Results. Dietary I3C increased plasma renin activity (PRA), plasma Ang II levels, and arterial BP in a dose-dependent manner. Induction of different fixed levels of renin gene expression and PRA produced hypertensive phenotypes of varying severity with rats developing either mild or malignant forms of hypertensive disease. Administration of I3C, at a dose of 0.15% (w/w), induced a slowly developing form of hypertension whereas administration of a higher dose (0.3%) induced a more rapidly developing hypertension and the clinical manifestations of malignant hypertension including severe weight loss. Both hypertensive phenotypes were characterised by reduced renal plasma flow, increased filtration fraction, elevated PRA, and increased plasma and intrarenal Ang II levels. These I3C-induced changes in renal haemodynamics, PRA and kidney Ang II levels were more pronounced in Cyp1a1-Ren2 rats with malignant hypertension. Chronic administration of the AT 1 -receptor antagonist,

show abstract

Arterial Hypertension in Diabetes: Etiology and Treatment

Bakris

Tarif²,

Black

2003

International Textbook of Diabetes Mellitus

View full text Add to dashboard Cite

Hypertension is highly prevalent among people with diabetes, especially those with type 2 diabetes. While the genesis of hypertension in diabetes is multifactorial, it is clear that early dysfunction of the vasculature, related, in part, to abnormalities in modulation of vascular tone by nitric oxide, heralds development of hypertension in such individuals. Presence of hypertension substantially increases the risk of adverse outcomes with regard to both the CV and renal systems. Once nephropathy becomes manifest, i.e. elevation in serum creatinine and macroalbuminuria, lowering of blood pressure to the recommended guideline goals slows kidney disease progression and reduces CV risk to a greater extent than does glucose control. Based on recent guidelines if systolic blood pressure is >15–20 mmHg above the goal, two drugs should be started, one of which should to be a diuretic. Clearly, angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers have also demonstrated benefits in these patients when used in concert with diuretics. The positive outcomes with diuretics relates clearly to their ability to lower blood pressure, especially in volume‐expanded individuals, which is true of virtually all people with diabetes because of the effects of insulin on proximal tubular sodium reabsorption.

show abstract

Renal Accumulation of Circulating Angiotensin II in Angiotensin II–Infused Rats

Cited by 100 publications

References 20 publications

Intrarenal Angiotensin II Augmentation in Angiotensin II Dependent Hypertension.

Intrarenal Angiotensin II Augmentation in Angiotensin II Dependent Hypertension.

Genetic Clamping of Renin Gene Expression Induces Hypertension and Elevation of Intrarenal Ang II Levels of Graded Severity in Cyp1a1-Ren2 Transgenic Rats

Arterial Hypertension in Diabetes: Etiology and Treatment

Contact Info

Product

Resources

About