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 journalArticlepeer-review

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

Keywords

  • Candidate genes
  • Endothelium
  • Stroke

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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