Does the kidney play a role in the aetiology of primary hypertension? Evidence from renal transplantation studies in rats and humans.
In renal cross-transplantation studies between four different strains of genetically hypertensive rats including Dahl salt-sensitive hypertensive rats, Milan hypertensive rats, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) on the one hand and their respective normotensive control strains on the other hand, it was found that BP determinants were carried within the kidney. To determine whether post-transplantation hypertension in recipients of an SHRSP kidney was due to a primary or secondary defect in the renal graft, hypertension in SHRSP kidney donors was prevented by chronic antihypertensive drug treatment. Despite sustained BP normalisation in SHRSP kidney donors, the recipients developed post-transplantation hypertension. This finding indicates that SHRSP kidneys carry a primary defect which can elicit hypertension. F1 hybrids bred from SHRSP and normotensive Wistar-Kyoto rat (WKY) parents show an age-related increase in arterial BP up to borderline hypertensive levels. Renal transplantation studies in young rats indicate that the development of borderline hypertension in (SHRSP x WKY)-F1 hybrids can be blunted by bilateral nephrectomy and transplantation of a WKY kidney. Clinical studies in human renal transplant patients also indicate that the genetic background of the kidney donor with respect to predisposition for genetic hypertension significantly influences BP and/or the need for antihypertensive medication in the recipients. Together, the results of renal transplantation studies in animals and humans suggest that a genetic defect in the kidney plays a major role in the pathogenesis of primary hypertension.
Department of Pharmacology, University of Heidelberg, Germany.
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D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY