Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.

Abstract

The spontaneously hypertensive rat (SHR) exhibits alterations in the renin-angiotensin-aldosterone system which are similar to those that characterize patients with "nonmodulating" hypertension, a common and highly heritable form of essential hypertension. Accordingly, we determined whether the inheritance of a DNA restriction fragment length polymorphism (RFLP) marking the renin gene of the SHR was associated with greater blood pressure than inheritance of a RFLP marking the renin gene of a normotensive control rat. In an F2 population derived from inbred SHR and inbred normotensive Lewis rats, we found the blood pressure in rats that inherited a single SHR renin allele to be significantly greater than that in rats that inherited only the Lewis renin allele. To the extent that the SHR provides a suitable model of "nonmodulating" hypertension, these findings raise the possibility that a structural alteration in the renin gene, or a closely linked gene, may be a pathogenetic determinant of increased blood pressure in one of the most common forms of essential hypertension in humans. (J. Clin. Invest. 1990Invest. . 85:1328Invest. -1332 hypertension.

Genetic epidemiology of essential hypertension

“…For example, in strains of Dahl-S and spontaneously hypertensive rats (believed to be the experimental counterpart of human essential hypertension), investigators have linked blood pressure to the genes for renin, angiotensin-converting enzyme (ACE) and atrial natriuretic peptide receptor. [22][23][24][25] However, several linkage and association studies of the human renin and ACE loci have given negative results, [26][27][28][29][30][31] except for one study in a black population, which found a possible association between blood pressure and a restriction fragment length polymorphism (RFLP) in the renin gene. 32 The SA gene has also shown some promise as a candidate gene for hypertension.…”

Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spontaneously hypertensive rat.

“…Although this strain has been the subject of extensive physiologic and biochemical investigation, little is known about the primary genetic lesions responsible for the pathogenesis of spontaneous hypertension. Recent linkage studies in recombinant inbred strains and in F2 populations derived from the SHR and normotensive strains have suggested that BP quantitative trait loci (QTLs) may exist on chromosomes 1, 2, 4, 8, 10, 13, 16, 19, and 20 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, the individual contributions of each of these chromosomes in the pathogenesis of spontaneous hypertension have not been clearly defined.…”

The Kidney Androgen-regulated Protein Promoter Confers Renal Proximal Tubule Cell-specific and Highly Androgen-responsive Expression on the Human Angiotensinogen Gene in Transgenic Mice

“…In blood, renin proteolytically cleaves AGT to form angiotensin I (Ang-I) which is further processed by angiotensin converting enzyme to form Ang-II, a potent vasoconstrictor and antinatriuretic peptide. The RAS has been implicated in the genetic basis of hypertension and pre-eclampsia (1)(2)(3)(4). Our understanding of the RAS in normal and pathophysiological regulation of blood pressure has been complicated by the fact that in addition to its actions as an endocrine system, certain individual tissues, such as the kidney (5-7), heart (8, 9), brain (10), and vasculature (11), contain all the components of the RAS cascade and therefore have the potential for local synthesis and action of Ang-II.…”