A Possible Primary Role for the Kidney in Essential Hypertension

Abstract

The role of the kidney in "essential" or "genetic" types of hypertension has been evaluated both in a rat model such as the Milan hypertensive strain (MHS) or in humans. In both species, abnormalities of renal function have been demonstrated before the development of hypertension. Moreover hypertension could be "transplanted" with the kidney when kidney cross-transplantation was carried out between MHS and the Milan normotensive strain (MNS). Also in humans, the familiality for hypertension of the donor affected the requirement of antihypertensive therapy of the recipient. Further studies furnished results that were consistent with the hypothesis that a primary increase in Na transport across the tubular cell could be responsible for the pressor effect of the kidney in MHS or in humans. Because many similarities were found between the function of the tubular cell and the red blood cell in MHS, red blood cells were used to gain information about the molecular genetic mechanisms underlying these cellular changes. The results so far obtained showed that red blood cell abnormalities in MHS were genetically determined within the stem cells and genetically associated with the development of hypertension in F2 hybrids obtained by crossing the F1 (MHS X MNS). Moreover, the abnormal Na transport across the cell membrane may be due to an abnormal function of the membrane skeleton proteins. Studies are in progress to evaluate a possible cause-effect relationship between: membrane skeleton protein-ion transport across the cell membrane and the development of hypertension.

Renal medullary effects of transient prehypertensive treatment in young spontaneously hypertensive rats

“…The kidney plays a crucial role in BP regulation and the development of hypertension (Bianchi et al. 1974, 1989, Rettig et al.…”

“…It is well established that the kidney plays a central role (Bianchi et al. 1974, 1989, Guidi et al.…”

Crosstransplantation of kidneys in normal and Hyp mice. Evidence that the Hyp mouse phenotype is unrelated to an intrinsic renal defect.

“…The technique of organ crosstransplantation has been used previously to distinguish whether the phenotypic and/or biochemical characteristics of a variety of genetic diseases result from innate defects in end-organ function and/or systemic hormonal/metabolic influences. Such investigations have identified an intrarenal abnormality as a primary defect in a genetic form of hypertension in the rat (26), and an intrahepatic defect as causal of deranged uric acid metabolism in Dalmation dogs (27). In contrast, alterations in the affected host environment have been determined as the primary cause of resistance to arteriosclerosis in pigs with von Willebrand's disease (28), and as primary or coexistent abnormalities in avian muscular dystrophy (29).…”

Role of the Gly460Trp polymorphism of the α-adducin gene in primary hypertension in Scandinavians

“…3 It has been shown that the Milan hypertensive rat (MHS) 4 and a subgroup of humans with hypertension have enhanced transmembranic ion transport, an effect possibly involving the cytoskeleton. [5][6][7][8] Genetic differences in renal tubular salt reabsorption could thus contribute to the development of hypertension. [9][10][11][12][13][14] Cross-immunisation of cytoskeleton proteins between MHS and the normotensive rat strain (MNS) revealed immunochemical differences in an ␣/␤ heterodimeric protein called adducin.…”