Analysis of the genetic basis of the endothelium-dependent impaired vasorelaxation in the stroke-prone spontaneously hypertensive rat: A candidate gene approach

Speranza Rubattua, Rosangela Giliberti, Rosaria Russo, Bruna Gigante, Ursula Ganten, Massimo Volpe

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Objective. To investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr). Design and methods. An SHRsp/SHRsr F 2-intercross (n = 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment, the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT(1b) receptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included. Results. The endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F 2 descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype. Conclusion. A candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality. (C) Lippincott Williams and Wilkins.

Original languageEnglish
Pages (from-to)161-165
Number of pages5
JournalJournal of Hypertension
Volume18
Issue number2
Publication statusPublished - 2000

Fingerprint

Inbred SHR Rats
Vasodilation
Endothelium
Blood Vessels
Stroke
Genes
Phenotype
Atrial Natriuretic Factor Receptors
Adrenomedullin
Angiotensinogen
Kallikreins
Nitric Oxide Synthase Type III
Brain Natriuretic Peptide
Endothelins
Atrial Natriuretic Factor
Peptidyl-Dipeptidase A
Vasoconstriction
Renin
Angiotensin II
Acetylcholine

Keywords

  • Candidate genes
  • Endothelium
  • Stroke

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Analysis of the genetic basis of the endothelium-dependent impaired vasorelaxation in the stroke-prone spontaneously hypertensive rat : A candidate gene approach. / Rubattua, Speranza; Giliberti, Rosangela; Russo, Rosaria; Gigante, Bruna; Ganten, Ursula; Volpe, Massimo.

In: Journal of Hypertension, Vol. 18, No. 2, 2000, p. 161-165.

Research output: Contribution to journalArticle

@article{bbdf2cb15869491c890ef5e7589e712d,
title = "Analysis of the genetic basis of the endothelium-dependent impaired vasorelaxation in the stroke-prone spontaneously hypertensive rat: A candidate gene approach",
abstract = "Objective. To investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr). Design and methods. An SHRsp/SHRsr F 2-intercross (n = 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment, the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT(1b) receptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included. Results. The endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F 2 descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype. Conclusion. A candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality. (C) Lippincott Williams and Wilkins.",
keywords = "Candidate genes, Endothelium, Stroke",
author = "Speranza Rubattua and Rosangela Giliberti and Rosaria Russo and Bruna Gigante and Ursula Ganten and Massimo Volpe",
year = "2000",
language = "English",
volume = "18",
pages = "161--165",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Analysis of the genetic basis of the endothelium-dependent impaired vasorelaxation in the stroke-prone spontaneously hypertensive rat

T2 - A candidate gene approach

AU - Rubattua, Speranza

AU - Giliberti, Rosangela

AU - Russo, Rosaria

AU - Gigante, Bruna

AU - Ganten, Ursula

AU - Volpe, Massimo

PY - 2000

Y1 - 2000

N2 - Objective. To investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr). Design and methods. An SHRsp/SHRsr F 2-intercross (n = 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment, the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT(1b) receptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included. Results. The endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F 2 descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype. Conclusion. A candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality. (C) Lippincott Williams and Wilkins.

AB - Objective. To investigate the role of potential candidate genes in the pathogenesis of the endothelium-dependent impaired vasorelaxation that associates and co-segregates with stroke in the stroke-prone spontaneously hypertensive rat (SHRsp) compared with the stroke-resistant SHR (SHRsr). Design and methods. An SHRsp/SHRsr F 2-intercross (n = 137; 64 males, 73 females) was obtained and, at the age of 6 weeks, it was placed under a stroke permissive Japanese-style diet for 4 weeks. At the end of the treatment, the vascular function of each rat was characterized. The maximal vasorelaxation to acetylcholine after maximal vasoconstriction (delta ratio) was considered as the quantitative phenotype. The following candidate genes were related to the delta ratio: renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II AT(1b) receptor, atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic peptide GC-A receptor, kallikrein, endothelial nitric oxide synthase. In addition, polymorphic markers located inside areas of the rat genome where other candidates (i.e. adrenomedullin, endothelin, Ang II AT1a receptor) are known to map were included. Results. The endothelial vascular dysfunction of the SHRsp showed a variable distribution among SHRsp/SHRsr F 2 descendants, independently from the blood pressure levels. A genotype/phenotype co-segregation analysis for each of the genes tested did not show any statistically significant co-segregation with the vascular phenotype. Conclusion. A candidate gene approach used to investigate the genetic basis of the endothelial-dependent vascular dysfunction of the SHRsp strain did not reveal any evidence to support the hypothesis that the genes tested play any role in the pathogenesis of the stroke-related vascular abnormality. (C) Lippincott Williams and Wilkins.

KW - Candidate genes

KW - Endothelium

KW - Stroke

UR - http://www.scopus.com/inward/record.url?scp=0033996602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033996602&partnerID=8YFLogxK

M3 - Article

C2 - 10694183

AN - SCOPUS:0033996602

VL - 18

SP - 161

EP - 165

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 2

ER -