Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link.

Abstract

The significance of the erythrocyte abnormalities described in rats and humans with spontaneous hypertension is far from clear. This study, in two highly inbred strains of rats, was designed to evaluate whether these abnormalities are primary and thus genetically related to hyper-tension. The Milan hypertensive strain (MHS) and its normotensive control strain (MNS) were used to carry out two types of experiments. In two groups of lethally irradiated (MHS x MNS) F, hybrids, bone marrow from MHS or MNS was transplanted. The differences in red cell function between the recipients of bone marrow from MHS and recipients of bone marrow from MNS were similar to those existing between the parental donor MHS and MNS: Na +-K + cotransport was increased (p < 0.02) and intracellular Na + content (p < 0.05) and cell volume (p < 0.02) were decreased in MHS. The same pattern was observed when this experiment was repeated in different groups of F, hybrids. In individuals of the segregating F 2 population, obtained by crossing the (MHS x MNS) F, hybrids, there was a positive correlation (p < 0.001) between the red blood cell Na +-K + cotransport and the mean blood pressure. These results indicate that the erythrocyte abnormalities may well be genetically associated with the primary cause of spontaneous hypertension in rats. Because of the many similarities demonstrated when young prehypertensive MHS or humans prone to develop hypertension are compared with their respective controls, it is possible that the findings described here in rats are relevant to human essential hypertension. (Hypertension 7: 319-325, 1985) KEY WORDS • red blood cell • genetic hypertension • cell volume • ion transport T HE cause of essential hypertension is not known. It is generally accepted that hyperten-sion develops when there is increased genetic sensitivity to certain environmental stimuli 1 and that red blood cell (RBC) membrane functions are abnormal in humans with essential hypertension 2 " 6 and rats with spontaneous hypertension. 7 '" It is not clear whether these alterations in red cell cation transport are the result of chance genetic selection unrelated to the cause of hypertension, are secondary to the hyperten-sive disease, or are the direct phenotypic expression of the same genetic abnormalities responsible for the increased susceptibility to hypertension. We must determine which of these possibilities is responsible if we wish to use the RBC transport systems as probes to study the genetic mechanisms of arterial hypertension. We have approached these questions by using two highly inbred strains of rats, the Milan hypertensive strain (MHS, inbreeding coefficient 0.988) and its nor-motensive control (MNS, inbreeding coefficient 0.989). Previous studies 12 " 14 with MHS and MNS showed many pathophysiological similarities between their hypertension and essential hypertension in humans. Kidney cross-transplantation and renal function studies suggested that the hypertension of MHS might originate from a primary increase in the transport of Na...

Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets.

“…An increased platelet membrane microviscosity has been described in spontaneously hypertensive rats and ascribed either to protein (32) or to fatty acid (33) constituents of the membrane. The fatty acid contents of platelet and red cell membranes appear to be genetically determined and associated with either a family history or the development of hypertension in rats and men (34,35). Exactly how these membrane alterations interact with agonist-mediated adrenergic receptor desensitization and whether they may be the source ofthe defect identified in human essential hypertension remains to be elucidated.…”

Membrane Ion Transport in Erythrocytes of Salt Hypertensive Dahl Rats and Their F2 Hybrids: the Importance of Cholesterol

“…Altered activity of the Na -K pump and/or Na -K cotransport system (HTG) (15,16). Genetic analysis based upon F2 hybrids or recombinant inbred strains revealed a significant cosegregation of blood pressure with abnormal Na -K cotransport (13,17) or enhanced Na leak (15,18).…”

Development of genetic hypotheses in essential hypertension

“…On the assumption that the underlying molecular determinant was ubiquitous, the investigation was extended to other cell types. In erythrocytes, significant differences in Na ϩ -K ϩ co-transport between the two strains were reported that cosegregated with arterial pressure in appropriate genetic crosses (Bianchi et al 1985).…”