Reversal of Microvascular Rarefaction and Reduced Renal Mass Hypertension

Rieder, Mark J.; Roman, Richard J.; Greene, Andrew S.

doi:10.1161/01.hyp.30.1.120

Cited by 54 publications

(42 citation statements)

References 24 publications

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“…The method used for measurements of PRA was performed as previously described (45). Briefly, arterial blood was collected in tubes containing K 3EDTA and immediately centrifuged at 1500 g and 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…The samples were thawed on ice, and neomycin sulfate (0.1%), phenylmethylsulfonyl fluoride (0.25%), and maleic anhydrate (0.2 mol/l) were added to 50 l of sample to inhibit converting enzyme and protease activity. After generation ANG I concentration was determined by radioimmunoassay (45).…”

Section: Methodsmentioning

confidence: 99%

“…The generation of the congenic strains combined with the pharmacological studies provides new insight into how renin regulates microvascular density in skeletal muscle and strongly suggested that RAS disregulation plays a critical role in the attenuation of the microvascular angiogenesis in the saltsensitive hypertensive SS/Mcwi rat. Understanding how disregulation of renin impacts angiogenesis in the SS/Mcwi rat may shed light on the reduction in vessel density that occurs in several forms of low-renin hypertension in humans (25,31,45).…”

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confidence: 99%

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Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Resende

Amaral

Moreno

et al. 2008

Physiological Genomics

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de Resende MM, Amaral SL, Moreno C, Greene AS. Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation. Physiol Genomics 33: 33-40, 2008. First published January 15, 2008 doi:10.1152/physiolgenomics.00150.2007.-Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13 BN /Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13 BN /Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS. renin-angiotensin system; chromosomal substitution THE IMPORTANCE of the renin-angiotensin system (RAS) in controlling sodium homeostasis and vascular resistance is well established; however, in the past decade, much attention has been focused on the importance of angiotensin II (ANG II) as a regulator of microvessel density. Studies from our laboratory (2-4, 15, 37, 42) over the last 5 years have shown that ANG II is an essential component of the control system regulating microvessel density in the skeletal muscle. We have shown that inhibition of RAS activity with the use of pharmacological blockers of ANG II formation and blockade of the angiotensin type 1 (AT 1 ) receptor significantly attenuated the skeletal muscle angiogenic response of normotensive rats induced by exercise (3) and electrical stimulation (2). In addition, we found (37) that chronic infusion of ANG II, at subpressor doses, completely restored the angiogenesis response induced by electrical stimulation in rats fed a high-salt diet. The effects of high salt on microvascular structure and function in the absence of hypertension have been largely attributed to the suppress...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Resende

Amaral

Moreno

et al. 2008

Physiological Genomics

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“…Properly diluted enzyme samples (10 l) were individually incubated with ANG I (36 M) for 30 min in a final volume of 100 l TBS, and the reactions were terminated by heating at 100°C for 3 min. The ANG II formed after HPLC separation from other components of the reaction mixture was measured by RIA, as previously described (49). A standard curve for ANG II, ranging from 0.32 to 82.5 fmol, allowed quantification of the conversion reactions.…”

Section: Methodsmentioning

confidence: 99%

Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme

Santos

Caprio²,

Oliveira³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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. Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme. Am J Physiol Heart Circ Physiol 285: H775-H783, 2003. First published April 24, 2003 10.1152/ajpheart.00818. 2002We recently described a chymostatin-sensitive elastase-2 as the major angiotensin (ANG) II-forming enzyme in the perfusate of the rat mesenteric arterial bed (MAB) with the same cDNA sequence as rat pancreatic elastase-2. The role of this enzyme in generating ANG II was examined in the rat isolated and perfused MAB. The vasoconstrictor effect elicited by ANG I and the renin substrate tetradecapeptide was only partially inhibited by captopril but abolished by the combination of captopril and chymostatin or N-acetyl-AlaAla-Pro-Leu-chloromethylketone (Ac-AAPL-CK; inhibitor originally developed for human elastase-2). The effect induced by [Pro 11 ,D-Ala 12 ]-ANG I, an ANG I-converting enzyme (ACE)-resistant biologically inactive precursor of ANG II, was blocked by chymostatin or Ac-AAPL-CK. It was also demonstrated that cultured rat mesenteric endothelial cells synthesize elastase-2 and that mRNA for this enzyme can be detected in different rat tissues such as the pancreas, MAB, lung, heart, kidney, liver, and spleen. In conclusion, the demonstration of a functional alternative pathway to ACE for ANG II generation in the rat MAB and the fact that cultured MAB endothelial cells are capable of producing and secreting elastase-2 represent strong evidence of a physiological role for this enzyme in the rat vasculature. endothelium; chymostatin SEVERAL STUDIES HAVE POSTULATED the existence of alternative pathways to angiotensin (ANG)-converting enzyme (ACE) for ANG II generation in tissues of different species based on evidence derived from experiments carried out with a combination of protease inhibitors and ANG II receptor antagonists. In a pioneering study (9) in this area, it was demonstrated that the vasoconstrictor response induced by ANG I in blood vessels of the hamster cheek pouch was blocked only partially by ACE inhibitors but completely abolished by ANG II receptor antagonists, leading to the conclusion that this vascular bed converts significant amounts of ANG I to ANG II by a route that does not involve ACE. In other investigations, the partial or total blockade of ANG II formation by different combinations of ACE inhibitors with chymostatin or other protease inhibitors has provided clues as to the nature of the enzymes involved in ANG I conversion in a particular tissue or pharmacological preparation (23,45). Since the advent of [Pro 11 ,D-Ala 12 ]-ANG I, a biologically inactive precursor that selectively yields ANG II on incubation with chymases but not with ACE or carboxypeptidases (22), several reports (18,22,26,38,41,43,61,63) have described the relative contribution of chymases in ANG II formation in isolated preparations derived from various species.The vascular endothelium actively participates in the control of vascular tone through the synthesis and metabolism of seve...

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“…31 In order to determine whether kidney of anencephalic and normal fetuses is functional, the number, shape, size, and distribution of nephrons 32,33 and the total volume of the kidney 34 and its anatomical characteristics should be evaluated. 35,36 Although there are many studies investigating the features of the kidney 37,38 using stereological methods, there are few studies on kidney development 37,[39][40][41][42][43][44] and none of these specifically study anencephalic fetus kidneys.…”

Section: Discussionmentioning

confidence: 99%

Stereological Evaluation of the Kidneys of Anencephalic and Normal Fetuses

et al. 2011

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The aim of this study is to test the glomerular and other quantitative parameters of kidneys of anencephalic fetuses and comparing those to "normal" fetuses. In this study, 20 kidneys of human fetuses (5 boys and 5 girls of anencephalic fetus, and 5 boys and 5 girls of normal fetus), at gestational ages of 25-30 weeks, were examined. This study is based on two basic research methods: one is a conventional anatomical measurement at the macroscopical level; the other is a design-biased stereological method at the microscopical level. Physical dissector and Cavalieri principle were used to estimate the total and numerical density of glomerulus and the volume of kidney, respectively. The results of the two types of investigation were compared based on anencephalic/normal and boy/girl kidneys at both the macroscopical and microscopical levels. There was no significant difference found between the quantitative features of kidneys (volume of kidneys and mean number and/or height of glomerulus) belonging to anencephalic and normal fetuses. The results of this study suggest that anencephalic fetuses did not differ from normal fetuses in respect of kidneys.

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Reversal of Microvascular Rarefaction and Reduced Renal Mass Hypertension

Cited by 54 publications

References 24 publications

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Functional role, cellular source, and tissue distribution of rat elastase-2, an angiotensin II-forming enzyme

Stereological Evaluation of the Kidneys of Anencephalic and Normal Fetuses

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