Genetic heterogeneity of the spontaneously hypertensive rat.

Nabika, Toru; Nara, Yasuo; Ikeda, Katsumi; Yamori, Yukio

doi:10.1161/01.hyp.18.1.12

Cited by 86 publications

(42 citation statements)

References 13 publications

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“…It has become clear that rat genotypes vary according to source. 37 - 38 Arteries from normotensive rats showed a continuous relaxation response to intraluminally applied acetylcholine, whereas the responses in those from hypertensive rats were significantly reduced and, at the highest concentration used (10~5 mol/L), SHR arteries reconstricted. This effect was endothelium mediated, because after removal of the endothelium acetylcholine did not elicit further constriction in preconstricted arteries of SHR.…”

Section: Discussionmentioning

confidence: 92%

In vitro perfusion studies of resistance artery function in genetic hypertension.

Falloon¹,

Bund²,

Tulip³

et al. 1993

Hypertension

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To examine the function of resistance-sized arteries in hypertension under in vitro conditions that approximate in Wvo conditions as much as possible, we mounted segments of second-order mesenteric resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats aged 12 to 13 weeks in a perfusion myograph and exposed them to conditions of constant flow and pressure. The endothelial integrity was validated both functionally and histologically. Vascular sensitivity to norepinephrine was examined when the hormone was applied either intraluminally or extraluminally and before and after removal of the endothelium. Both endothelium-dependent and -independent dilatation was assessed by the intraluminal application of acetylcholine and sodium nitroprusside, respectively. Sodium nitroprusside was applied to arteries after endothelium removal. Arterial responses were measured by changes in intraluminal diameter recorded with a video camera and imaging system. Vessels from SHR demonstrated depressed endothelium-dependent relaxation but similar endotheliumindependent relaxation and greater sensitivity to norepinephrine with both intraluminal and extraluminal application. Removal of the endothelium abolished the differences in sensitivity to norepinephrine between the two strains. The results demonstrate that resistance arteries from SHR when examined under in vitro perfusion display enhanced sensitivity to norepinephrine due to depressed endotheliumdependent dilatation, and the data suggest that functional modifications in the endothelium may play an important role in hypertensive vascular disease. (Hypertension. 1993;22:486-495.) KEY WORDS • endothelium • norepinephrine • acetylcholine • nitroprusside • vascular resistance • hypertension, genetic • rats, inbred SHR

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Section: Discussionmentioning

confidence: 92%

In vitro perfusion studies of resistance artery function in genetic hypertension.

Falloon¹,

Bund²,

Tulip³

et al. 1993

Hypertension

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“…These not fully inbred stocks were imported by the National Institutes of Health in the United States. 16,156 Subsequently, several colonies were established, which lack genetic homogeneity and thus show phenotypic variance. 16,[156][157][158] …”

Section: Strain Characteristicsmentioning

confidence: 99%

Mapping genetic determinants of kidney damage in rat models

Schulz

Kreutz

2012

Hypertens Res

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During the last two decades, significant progress in our understanding of the development of kidney diseases has been achieved by unravelling the mechanisms underlying rare familial forms of human kidney diseases. Due to the genetic heterogeneity in human populations and the complex multifactorial pathogenesis of the disease phenotypes, the dissection of the genetic basis of common chronic kidney diseases (CKD) remains a difficult task. In this regard, several inbred rat models provide valuable complementary tools to uncover the genetic basis of complex renal disease phenotypes that are related to common forms of CKD. In this review, data obtained in nine experimental rat models, including the Buffalo (BUF), Dahl salt-sensitive (SS), Fawn-hooded hypertensive (FHH), Goto-Kakizaki (GK), Lyon hypertensive (LH), Munich Wistar Frömter (MWF), Sabra hypertension-prone (SBH), spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) inbred strains, that contributed to the genetic dissection of renal disease phenotypes are presented. In this panel of inbred strains, a large number of quantitative trait loci (QTL) linked to albuminuria/proteinuria and other functional or structural kidney abnormalities could be identified by QTL mapping analysis and follow-up studies including consomic and congenic rat lines. The comprehensive exploitation of the genotype-renal phenotype associations that are inherited in this panel of rat strains is suitable for making a significant contribution to the development of an integrated approach to the systems genetics of common CKD. INTRODUCTIONCommon forms of chronic kidney diseases (CKD) represent complex disease phenotypes that are influenced by both environmental and genetic factors. [1][2][3][4][5] Both arterial hypertension and type-2 diabetes mellitus are major contributors to complex CKD, which has a high prevalence in the general human population worldwide affecting B11-15% of individuals in Europe and United States. 6-9 CKD represents as expected a major risk factor for the progression to end-stage renal disease but associates also with an increased risk of cardiovascular morbidity and mortality. 10,11 In addition to the assessment of impaired renal function or glomerular filtration rate, urinary albumin excretion rate (albuminuria) represents another important clinical marker for the evaluation of CKD and cardiovascular risk of patients. [10][11][12][13][14][15] These renal disease phenotypes are also inherited in several inbred rat strains many of which are hypertensive. 16 During the last decades, genetic mapping studies by genome-wide linkage analysis followed by fine mapping of selected quantitative trait loci (QTL) for renal disease phenotypes were reported. Subsequently, studies in consomic and congenic rats were performed to further unravel the genetics of kidney injury in inbred rat strains. For QTL confirmation, consomic strains were generated by transfer of an entire chromosome carrying a QTL from a donor strain into the disease backgro...

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“…All experiments were performed in male SHR (12 weeks old; n =18) obtained from the Disease Model Cooperative Research Association (Kyoto, Japan) (16). The experimental protocol was approved by the Committee on the Ethics of Animal Experimentation of the Faculty of Medicine, Kyushu University.…”

Section: Icy Treatmentmentioning

confidence: 99%