Influence on Blood Pressure of Renal Isografts between Spontaneously Hypertensive and Normotensive Rats, Utilizing the F&lt;sub&gt;1&lt;/sub&gt; Hybrids

Kawabe, Kazuki; Watanabe, Takushi X.; Shiono, Kumiko; Sokabe, Hirofumi

doi:10.1536/ihj.19.886

Cited by 146 publications

(55 citation statements)

References 18 publications

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“…2 The spontaneously hypertensive strain of rats develops elevated arterial pressure spontaneously with age, and in some strains this hypertension is exacerbated with elevated sodium chloride intake. Kawabe et al 3 have shown that in this strain, replacement at an early age of the SHR kidneys by transplantation with kidneys from age-matched normotensive control rats results in a substantial diminution of the blood pressure. This same response has been shown in other genetic models of hypertension including the Milan hypertensive strain 4 and the DS rat.…”

Section: Renal Function and Arterial Pressurementioning

confidence: 88%

Relation between sodium intake, renal function, and the regulation of arterial pressure.

Osborn

1991

Hypertension

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The long-term regulation of arterial pressure requires the maintenance of a balance between sodium and water intake and sodium and water excretion. Normal salt and water balance leads to stable body fluid volumes and the maintenance of normal renal function is critical to establishing extracellular fluid volume homeostasis. This review focuses on the role of the kidney in the long-term control of salt and water balance with particular emphasis on the relations between sodium intake, the renin-angiotensin-aldosterone system, renal sympathetic nerve activity, and the regulation of arterial pressure via renal sodium and water excretion. T he regulation of the extracellular fluid volume encompasses the continuous, ongoing maintenance of normal sodium and water balance as a relation between sodium intake and excretion. As humans, we exist as intermittent sodium and water consumers, leaving the bulk of the task of regulating our constant expansion of extracellular fluid volumes to the renal excretory processes. There are many factors that influence renal sodium excretion and thereby participate in this regulatory process. These factors can be subdivided into extrinsic and intrinsic mechanisms. Extrinsic mechanisms include the production of angiotensin II (Ang II) and aldosterone, the release of atrial natriuretic factor, and the alterations of renal sympathetic outflow; some intrinsic mechanisms are the regulation of glomerular filtration rate, renal hemodynamics, intrarenal physical forces controlling tubular reabsorp- Supported by an American Heart Association Established Investigator Award, by an American Heart Association Grant-inAid, and by National Heart, Lung, and Blood Institute grants HL-40137 and HL-29587.Address for correspondence: Jeffrey L. Osborn, PhD, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226. tion, and intrarenal hormonal systems such as kinins, Ang n, and prostaglandins. Renal Function and Arterial PressureA close correlation between normal kidney function and blood pressure control has been demonstrated in several experimental forms of hypertension including the spontaneously hypertensive rat (SHR) 1 and the Dahl salt-sensitive (DS) rat.2 The spontaneously hypertensive strain of rats develops elevated arterial pressure spontaneously with age, and in some strains this hypertension is exacerbated with elevated sodium chloride intake. Kawabe et al 3 have shown that in this strain, replacement at an early age of the SHR kidneys by transplantation with kidneys from age-matched normotensive control rats results in a substantial diminution of the blood pressure. This same response has been shown in other genetic models of hypertension including the Milan hypertensive strain 4 and the DS rat. 5 Thus, a direct correlation has been documented between renal function and arterial pressure in several genetic models of hypertension, and in some strains a critical interaction exists between sodium intake and the magnitude of the hypertension.The complex relations between the natriu...

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Section: Renal Function and Arterial Pressurementioning

confidence: 88%

Relation between sodium intake, renal function, and the regulation of arterial pressure.

Osborn

1991

Hypertension

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“…37 All this accumulated evidence suggests that abnormalities in renal function may be involved in the pathogenesis of hypertension in SHR, more so when kidneys transplanted from SHR into Fl hybrids significantly raise blood pressure in the latter. 38 SHR are known to respond with exaggerated natriuresis when challenged with an acute sodium load 353940 ; however, this response is abolished when renal perfusion pressure is acutely reduced to normotensive levels, 40 -42 mainly through a decrease in the glomerular filtration rate. 40 This characteristic suggests that the kidneys of adult SHR require a higher blood pressure than those of their normotensive controls to excrete an acute sodium load.…”

Section: Discussionmentioning

confidence: 99%

Glomerular atrial natriuretic factor receptors in spontaneously hypertensive rats.

et al. 1989

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There are differences in the renal handling of sodium between spontaneously hypertensive rats (SHR) and their normotensive controls. We investigated whether this difference may be associated with changes in plasma and tissue atrial natriuretic factor (ANF) levels and with alterations in glomerular ANF receptors at 4, 8, 12, and 16 weeks of age. Age-matched Wistar-Kyoto (WKY) and Wistar rats were used as normotensive controls. Systolic blood pressure was higher in SHR at 8, 12, and 16 weeks, and cardiac hypertrophy was also present in these animals at 4 weeks. Plasma ANF C-and N-terminal concentrations were greater than in both normotensive groups at 8 and 16 weeks. ANF in the right atrium was higher in SHR than in WKY rats and identical to that in the Wistar group at 4 and 8 weeks. ANF in the left atrium was lower in SHR than in both control groups at week 12. No differences were found in ventricular ANF content. The density of glomerular ANF binding sites increased with age in WKY and Wistar rats but not in SHR. At weeks 8, 12, and 16, both normotensive groups had a higher density of binding sites than SHR, but binding site affinity was greater in SHR at weeks 8 and 12. After incubation with increasing concentrations of ANF, the production of cyclic guanosine monophosphate (cGMP) by isolated glomeruli from 16-week-old rats was lower in SHR than in both normotensive groups. We conclude that the development of hypertension in SHR is associated with higher plasma ANF levels and decreased glomerular ANF receptor density and glomerular cGMP production. Through modulation of ANF glomerular receptors, ANF in SHR, when compared with normotensive counterparts, may contribute to the difference in renal sodium handling. (Hypertension 1989; 13:567-574)

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“…14 For most of the BP QTLs, little data exist as to the tissue specificity of the BP effect. Although previous findings from transplantation studies involving SHR and WKY suggest that the kidney plays a primary role in hypertension, [15][16][17] its involvement in individual QTLs needs to be shown. In the present study, we take an important step forward with regard to the BP QTL region on RNO1, by providing direct evidence that a significant proportion of the phenotypic effect of the responsible BP genes in this region is mediated via the kidney.…”

Section: Discussionmentioning

confidence: 92%

Kidney Specificity of Rat Chromosome 1 Blood Pressure Quantitative Trait Locus Region

et al. 2002

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Abstract-Rat chromosome 1 has a region containing loci that influence blood pressure. In the present study, we investigated whether these loci mediate their effect via the kidney. Taking advantage of the histocompatability between a congenic strain (WKY.SHR-Sa, which contains the relevant chromosomal region from the spontaneously hypertensive rat) and its parental strain, the Wistar-Kyoto rat (WKY), we compared the effect of transplanting a kidney at 5 to 6 weeks of age from either congenic rats or WKY into bilaterally nephrectomized WKY. WKY.SHR-Sa animals and WKY with intact kidneys and with unilateral nephrectomy were studied as controls. Blood pressure was measured at 12, 16, 20, and 25 weeks of age. At all time points, blood pressure was significantly higher (by between 8 to 22 mm Hg, PϽ0.001) in 2-kidney WKY.SHR-Sa animals compared with WKY. This genotype-related difference was maintained in unilaterally nephrectomized rats. Most importantly, WKY that received transplants from WKY.SHR-Sa rats had significantly higher blood pressure (PϽ0.001 at all time points) compared with those that received transplants from other WKY. At any age, this difference was between 70% to 100% of the difference observed between the 1-kidney groups. There was no difference in plasma urea or creatinine between groups or evidence of chronic rejection in the cross-transplant group.The findings indicate that the major proportion of the blood pressure effect of loci on rat chromosome 1 is mediated through the kidney, and provide a rational basis for investigating genes located in the relevant chromosomal region and expressed in the kidney as likely candidates. Key Words: hypertension, experimental Ⅲ genetics Ⅲ rats, spontaneously hypertensive Ⅲ genes Ⅲ transplantation, renal I n the past decade, quantitative trait loci (QTLs) affecting blood pressure (BP) have been mapped to regions on several rat chromosomes by use of linkage analysis in segregating progeny from crosses of inbred hypertensive and normotensive rat strains. 1 In many instances, the presence of the QTLs has been confirmed by their capture in congenic strains. 1 These are strains in which a chromosomal region from one strain (eg, a hypertensive strain) is introgressed into another (eg, normotensive) strain by marker-selected backcrossing. 2 If the QTL is present in the introgressed segment, the congenic strain should have a different BP (higher in the above example) than that of the recipient parental strain.In previous studies, we 3 and others 1 have shown that a region in the midportion of rat chromosome 1 (RNO1) has Ն1 QTLs affecting BP. In second filial generation (F 2 ) progeny from a cross of the spontaneously hypertensive rat (SHR) and the Wistar-Kyoto rat (WKY) strains, the QTL region accounted for Ϸ25% of the variance in BP. 3 This segment of RNO1 is particularly interesting because it also harbors QTLs for stroke latency, 4 renal damage, 5 and diabetes-related phenotypes. 6 More recently, we have captured the region containing the BP QTL(s) in reciprocal conge...

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Influence on Blood Pressure of Renal Isografts between Spontaneously Hypertensive and Normotensive Rats, Utilizing the F<sub>1</sub> Hybrids

Cited by 146 publications

References 18 publications

Relation between sodium intake, renal function, and the regulation of arterial pressure.

Relation between sodium intake, renal function, and the regulation of arterial pressure.

Glomerular atrial natriuretic factor receptors in spontaneously hypertensive rats.

Kidney Specificity of Rat Chromosome 1 Blood Pressure Quantitative Trait Locus Region

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