Sympathetic Regulation of the Renal Functions in Rats Reciprocally Congenic for Chromosome 1 Blood Pressure Quantitative Trait Locus

Wang, Tao; Nabika, Toru; Notsu, Yoshitomo; Takabatake, Toshikazu

doi:10.1291/hypres.31.561

Cited by 10 publications

(18 citation statements)

References 41 publications

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“…Despite the reported differences in blood pressure between the SHRSP, SP.WKY Gla 2k and WKY strains [15], there was no difference in GFR between any strains, consistent with the literature [58,59]. Furthermore, eRPF was significantly lower in the SHRSP strain as compared to the WKY strain, as reported previously [59]. Importantly, eRPF in the SP.WKY Gla 2k strain was not different to that in the SHRSP strain, suggesting that the reduction in eRPF is not mediated by the chromosome 2 QTL examined.…”

Section: Discussionsupporting

confidence: 89%

“…It is highly significant, therefore, that the salt-sensitive hypertension of Dahl rats is blocked by the intracerebroventrocular infusion of trilostane, an inhibitor of 3bHSD activity [57]. Despite the reported differences in blood pressure between the SHRSP, SP.WKY Gla 2k and WKY strains [15], there was no difference in GFR between any strains, consistent with the literature [58,59]. Furthermore, eRPF was significantly lower in the SHRSP strain as compared to the WKY strain, as reported previously [59].…”

Section: Discussionsupporting

confidence: 79%

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Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

Sampson

Dashti

Beattie

et al. 2014

Journal of Hypertension

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 79%

Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

Sampson

Dashti

Beattie

et al. 2014

Journal of Hypertension

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“…A QTL that is closely linked to hypertension was found on chromosome 1 in stroke-prone SHR (SHRSP). 50, 51, 52 Based on this finding, Nabika and colleagues 53, 54, 55 at Shimane University established two congenic rat strains through 10 generations of repeated backcrossing. The ‘WKYpch1.0 congenic rat' was created by introgressing ‘the small QTL region (60-cM) for BP on rat chromosome 1 from SHRSP/Izm' into WKY/Izm rats (Figure 4).…”

Section: Quantitative Trait Locus (Qtl) On Chromosome 1 Affects the Ementioning

confidence: 98%

Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

et al. 2011

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Accentuated sympathetic nerve activity (SNA) is a risk factor for cardiovascular events. In this review, we investigate our working hypothesis that potentiated activity of neurons in the rostral ventrolateral medulla (RVLM) is the primary cause of experimental and essential hypertension. Over the past decade, we have examined how RVLM neurons regulate peripheral SNA, how the sympathetic and renin-angiotensin systems are correlated and how the sympathetic system can be suppressed to prevent cardiovascular events in patients. Based on results of whole-cell patch-clamp studies, we report that angiotensin II (Ang II) potentiated the activity of RVLM neurons, a sympathetic nervous center, whereas Ang II receptor blocker (ARB) reduced RVLM activities. Our optical imaging demonstrated that a longitudinal rostrocaudal column, including the RVLM and the caudal end of ventrolateral medulla, acts as a sympathetic center. By organizing and analyzing these data, we hope to develop therapies for reducing SNA in our patients. Recently, 2-year depressor effects were obtained by a single procedure of renal nerve ablation in patients with essential hypertension. The ablation injured not only the efferent renal sympathetic nerves but also the afferent renal nerves and led to reduced activities of the hypothalamus, RVLM neurons and efferent systemic sympathetic nerves. These clinical results stress the importance of the RVLM neurons in blood pressure regulation. We expect renal nerve ablation to be an effective treatment for congestive heart failure and chronic kidney disease, such as diabetic nephropathy.

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“…In contrast, reciprocal genetic effects like the one observed in the present study suggest a mendelian control of phenotypes: the genotype (or the haplotype) of a single gene (or a cluster of genes) had a major effect on the phenotype, independent of the genetic background. 21,22 Such a phenotype may be regulated by the gene(s) in a more direct manner and may be useful for speculating the functions of the gene(s).…”

Section: Iigaya Et Al Hyperactivity Of Rvlm In Congenic Ratsmentioning

confidence: 99%

Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla

Iigaya

Kumagai

Nabika³

et al. 2009

Hypertension

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Abstract-Genetic factors that induce essential hypertension have been examined using genome-wide linkage analyses. A quantitative trait locus (QTL) region that is closely linked to hypertension has been found on chromosome 1 in stroke-prone spontaneously hypertensive rats (SHRSPs). We used 2 congenic rats in which the blood pressure QTL on rat chromosome 1 was introgressed from SHRSP/Izm to Wistar-Kyoto (WKY)/Izm (WKYpch1.0) and from WKY/Izm to SHRSP/Izm (SHRSPwch1.0) rats by repeated backcrossing. Previous studies reported that the intermediate phenotype of this QTL for hypertension is characterized by the hyperactivity of the sympathetic nervous system in response to physiological and psychological stress. We performed intracellular patch-clamp recordings of rostral ventrolateral medulla (RVLM) neurons from WKY, WKYpch1.0, SHRSPwch1.0, and SHRSPs and compared the basal electrophysiological activities of RVLM neurons and the responses of these neurons to angiotensin II. The basal membrane potential of RVLM neurons from WKYpch1.0 was significantly "shallower" than that of the neurons from WKY. The depolarization of RVLM neurons from WKYpch1.0 in response to angiotensin II was significantly larger than that in neurons from WKY rats, whereas the depolarization of RVLM neurons from SHRSPwch1.0 was significantly smaller than that in neurons from SHRSPs. The response to angiotensin II of RVLM neurons from WKYpch1.0 and SHRSPs was sustained even after the blockade of all of the synaptic transmissions using tetrodotoxin. The QTL on rat chromosome 1 was primarily related to the postsynaptic response of RVLM bulbospinal neurons to brain angiotensin II, whereas both the QTL and other genomic regions influenced the basal activity of RVLM neurons. Key Words: sympathetic nervous system Ⅲ congenic rat Ⅲ angiotensin II Ⅲ stress Ⅲ RVLM neurons .T he stroke-prone spontaneously hypertensive rat (SHRSP) is a useful model for the study of human essential hypertension. 1 Previous genome-wide analyses identified a potent quantitative trait locus (QTL) on rat chromosome 1 (Chr-1) that is responsible for hypertension in SHRSPs; this trait was confirmed in congenic strains for the QTLs. [2][3][4][5] Further analyses of the congenic strains suggested that this QTL harbored a gene (or genes) that regulated sympathetic responses to various stresses, such as restraint, cold, and air-jet stress. [5][6][7] Because the stressors used were either physical or emotional in nature, we hypothesized that a common pathway regulating sympathetic responses to stress might be responsible for this phenomenon. In this regard, the genetic effects of the Chr-1 QTL on the neuronal activity of the rostral ventrolateral medulla (RVLM), which is thought to determine the basal sympathetic nervous tone in response to various inputs from higher brain centers, 8,9 were explored in this study. In addition, among various modulators of RVLM activity, we particularly focused on the role of angiotensin II (Ang II) based on the following observations: physiological studi...

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Sympathetic Regulation of the Renal Functions in Rats Reciprocally Congenic for Chromosome 1 Blood Pressure Quantitative Trait Locus

Cited by 10 publications

References 41 publications

Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

Introgressed chromosome 2 quantitative trait loci restores aldosterone regulation and reduces response to salt in the stroke-prone spontaneously hypertensive rat

Importance of rostral ventrolateral medulla neurons in determining efferent sympathetic nerve activity and blood pressure

Relation of Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 to Hyperactivity of Rostralventrolateral Medulla

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