Unraveling the Mystery of Goldblatt Hypertension

Navar, L. Gabriel; Zou, Long; Thun, Annette Von; Wang, Chi Tarng; Imig, John D.; Mitchell, Kenneth D.

doi:10.1152/physiologyonline.1998.13.4.170

Cited by 98 publications

(142 citation statements)

References 12 publications

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“…In the early stage of renovascular hypertension, renin secretion from the non-clipped kidney is reduced by the elevated perfusion pressure. 15 In contrast, the elevated pressure inhibits the processing of prorenin to renin, leading to accumulation of prorenin in renal juxtaglomerular cells, 16 and the tissue Ang II levels of the nonclipped kidneys rise gradually during the late stage of renovascular hypertension, 17 probably because of a prorenin-dependent mechanism. In the present study, activated prorenin and tissue Ang II levels were upregulated without any changes in (P)RR mRNA expression in the non-clipped kidneys.…”

Section: Long-term Effects Of Hrp On 2k1c Kidneys M Ryuzaki Et Almentioning

confidence: 99%

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

et al. 2010

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The handle region peptide (HRP), a (pro)renin receptor (P)RR blocker, did not prevent the acute nephropathy occurring 2 weeks after clipping in renovascular hypertensive rats. This study was performed to examine the effects of HRP, its scramble peptide, or a saline vehicle on slowly progressive nephropathy occurring in the kidneys of two-kidney, one-clip Goldblatt hypertensive rats. At 2 weeks after clipping, the renal morphology in the clipped and non-clipped kidneys was similar in the three groups of rats. At 12 weeks after clipping, however, the glomerulosclerosis index (GI) and the tubulointerstitial damage (TD) of the non-clipped kidneys of the HRP-treated rats were significantly lower than those of vehicle-treated rats, although the GI and the TD were similar in the rats treated with scramble peptide and vehicle. The GI and the TD of the clipped kidneys were similar in the three groups of rats at 12 weeks after clipping. In the non-clipped kidneys at 12 weeks after clipping, activated prorenin levels, angiotensin II levels and transforming growth factor (TGF)-b mRNA levels of HRP-treated rats were significantly lower than those of vehicle-treated rats, although they were similar in the non-clipped kidneys from the rats treated with scramble peptide and vehicle. In the clipped kidneys at 12 weeks after clipping, activated prorenin levels, angiotensin II levels and TGF-b mRNA levels were similar in the three groups of rats. These results suggest that the ((P)RR)-dependent activation of prorenin contributes to the pathogenesis of slowly progressive nephropathy in the intact kidney in a rat model of renovascular hypertension.

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Section: Long-term Effects Of Hrp On 2k1c Kidneys M Ryuzaki Et Almentioning

confidence: 99%

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

et al. 2010

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“…1 Previous studies have shown that activation of angiotensin II (ANG II) type 1 (AT 1 ) receptors predominantly mediates the effect of ANG II on the renal vasculature and is largely responsible for the development of hypertension in ANG II-dependent models of hypertension. [2][3][4] However, two subtypes for AT 1 receptors have been identified in mouse and rat (AT 1A and AT 1B ). 5 It has been demonstrated that the AT 1A receptors are the predominant subtype in most tissues, with the exception of the adrenal cortex, pituitary gland, and glomerulus, where the AT 1B receptors are also highly expressed.…”

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confidence: 99%

Essential Role of AT _1A Receptor in the Development of 2K1C Hypertension

et al. 2002

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Abstract-The aims of this study were to delineate the relative contribution of angiotensin II (ANG II) subtype 1A (AT 1A ) and 1B (AT 1B ) receptors to the development of two-kidney, one-clip (2K1C) Goldblatt hypertension in mice, to examine if increased nitric oxide synthase (NOS) activity counteracts the vasoconstrictor influences of ANG II in 2K1C hypertensive mice, and to determine the role of ANG II type 2 (AT 2 ) receptors in 2K1C hypertension in mice. AT 1A ANG II receptor knockout (AT 1A Ϫ/Ϫ) and wild-type (AT 1A ϩ/ϩ) mice underwent clipping of the right renal artery. Systolic blood pressure (SBP) was significantly lower in AT 1A Ϫ/Ϫ compared with AT 1A ϩ/ϩ mice, and neither clip placement nor AT 2 receptor blockade with PD 123319 (PD) altered SBP in AT 1A Ϫ/Ϫ mice. A significant and sustained rise in SBP from 119Ϯ5 to 163Ϯ6 mm Hg was observed in the 2K1C AT 1A ϩ/ϩ mice from day 10 to day 26. Chronic PD infusion did not alter the course of hypertension in 2K1C/AT 1A ϩ/ϩ. Acute PD infusion did not alter mean arterial Key Words: mice Ⅲ receptors, angiotensin II Ⅲ hypertension, renovascular Ⅲ nitric oxide synthase Ⅲ nitric oxide I t is well recognized that the renin-angiotensin system plays the pivotal role in the development and maintenance of two-kidney, one-clip (2K1C) Goldblatt hypertension. 1 Previous studies have shown that activation of angiotensin II (ANG II) type 1 (AT 1 ) receptors predominantly mediates the effect of ANG II on the renal vasculature and is largely responsible for the development of hypertension in ANG II-dependent models of hypertension. 2-4 However, two subtypes for AT 1 receptors have been identified in mouse and rat (AT 1A and AT 1B ). 5 It has been demonstrated that the AT 1A receptors are the predominant subtype in most tissues, with the exception of the adrenal cortex, pituitary gland, and glomerulus, where the AT 1B receptors are also highly expressed. 6,7 The critical role of AT 1A receptors in blood pressure (BP) regulation has been confirmed by the development of AT 1A receptor knockout mice (AT 1A Ϫ/Ϫ). The AT 1A Ϫ/Ϫ mice exhibit markedly lower BP and impaired ability for normal sodium handling by the kidney and urinary concentrating ability compared with their wild-type controls (AT 1A ϩ/ϩ). 8 -11 In contrast, the AT 1B receptor knockout mice (AT 1A Ϫ/Ϫ) exhibit no abnormal phenotype. 12 However, it has been shown that in the absence of AT 1A receptors, AT 1B receptors may partially replace the function of AT 1A receptors in BP regulation. 13 Moreover, it has been also demonstrated that when AT 1A receptors are absent, AT 1B receptors can play an important role in mediating ANG II effects in the renal vasculature. 14,15 Taken together, these results indicate that under certain conditions, AT 1B receptors partially compensate for the absence of AT 1A receptors. In view of this information, we hypothesized that activation of AT 1B might contribute to the development of 2K1C Goldblatt hypertension. Since the binding signatures of the AT 1A and AT 1B receptors are ident...

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“…The 2K1C hypertensive rat is a renovascular hypertensive model, which is characterized by elevated Ang II expression caused by ischemia in clipped kidney and shear stress in nonclipped kidney. The activity of RAS plays a key role in the development and maintenance of high BP through the production of Ang II [34,35] . Ang II has a high affinity for AT 1 receptors, which are responsible for Ang II-induced hypertension.…”

Section: Discussionmentioning

confidence: 99%

Effects of allisartan, a new AT1 receptor blocker, on blood pressure and end-organ damage in hypertensive animals

Yang

et al. 2009

Acta Pharmacol Sin

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Aim:To investigate the effects of allisartan, a new angiotensin II type 1 (AT 1 ) receptor antagonist, on blood pressure (BP) and end-organ damage (EOD) in hypertensive rats and dogs. Methods: First, a single dose of allisartan was given intragastrically to evaluate the BP reduction in spontaneously hypertensive rats (SHRs), two kidney-one clip (2K1C) renovascular hypertensive rats and dogs, and Beagle dogs with angiotensin II-induced hypertension. Second, allisartan was mixed in rat chow for long-term treatment. After 4 months of drug administration, rats were instrumented to determine BP and baroreflex sensitivity (BRS). Observation of morphologic changes was used to estimate EOD. Third, the acute toxicity of allisartan was compared with that of losartan in mice. Results: BP was significantly decreased after intragastric administration of allisartan in SHRs, 2K1C rats, 2K1C dogs and Beagle dogs with angiotensin II-induced hypertension. Compared with the control, SHRs that received long-term treatment with allisartan exhibited an improved BRS and organ protective effects. Mice who were administered allisartan experienced less acute toxicity than those treated with losartan. Conclusion: Allisartan is highly effective for BP reduction and organ protection with low toxicity.

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Unraveling the Mystery of Goldblatt Hypertension

Cited by 98 publications

References 12 publications

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

Essential Role of AT _1A Receptor in the Development of 2K1C Hypertension

Effects of allisartan, a new AT1 receptor blocker, on blood pressure and end-organ damage in hypertensive animals

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Unraveling the Mystery of Goldblatt Hypertension

Cited by 98 publications

References 12 publications

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

Involvement of activated prorenin in the pathogenesis of slowly progressive nephropathy in the non-clipped kidney of two kidney, one-clip hypertension

Essential Role of AT 1A Receptor in the Development of 2K1C Hypertension

Effects of allisartan, a new AT1 receptor blocker, on blood pressure and end-organ damage in hypertensive animals

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Essential Role of AT _1A Receptor in the Development of 2K1C Hypertension