Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies showed that erythrocytes from the Milan hypertensive strain of rats (MHS) are smaller and have a faster Na-K cotransport when compared with their normotensive controls (MNS). These characteristics are determined within the stem cell, are genetically associated with hypertension and are similar to other renal tubular cell abnormalities more directly involved in the development of hypertension in MHS. The difference in volume is maintained in ghost membranes, while the difference in transport is abolished in inside-out vesicles. Ghosts and cytoskeletons contain a 105-kilodalton protein already characterized by immunoblotting. This protein has been identified with erythrocyte adducin by several criteria, including binding to calmodulin and protein kinase C, phosphorylation and full immunological cross-reactivity with human adducin. Since only MHS rats immunized with MNS erythrocyte cytoskeletons produce anti-adducin antibodies, we suggest an immunogenic structural difference in adducin from the two strains, and an involvement of this difference in the alteration of Na-K cotransport observed.
 ...
PMID:Characterization of erythrocyte adducin from the Milan hypertensive strain of rats. 324 Dec

Environmental factors, genetic polymorphisms, and different experimental designs have been the main impediments to evaluating a genetic association between cell membrane cation transport abnormalities and human essential or genetic hypertension. We review the results obtained in the Milan hypertensive strain of rats (MHS) and in its appropriate control normotensive strain (MNS) to illustrate our approach to defining the role of cation transport abnormality in a type of genetic hypertension. Before the development of a difference in blood pressure between the two strains, the comparison of kidney and erythrocyte functions showed that MHS had an increased glomerular filtration rate and urinary output, and lower plasma renin and urine osmolality. Kidney cross-transplantation between the strains showed that hypertension is transplanted with the kidney. Proximal tubular cell volume and sodium content were lower in MHS while sodium transport across the brush border membrane vesicles of MHS was faster. Erythrocytes in MHS were smaller and had lower sodium concentration, and Na+-K+ cotransport and passive permeability were faster. The differences in volume, sodium content, and Na+-K+ cotransport between erythrocytes of the two strains persisted after transplantation of bone marrow to irradiated F1 (MHS X MNS) hybrids. Moreover, in normal segregating F2 hybrid populations there was a positive correlation between blood pressure and Na+-K+ cotransport. These results suggest a genetic and functional link in MHS between cell membrane cation transport abnormalities and hypertension. Thus erythrocyte cell membrane may be used for approaching the problem of defining the genetically determined molecular mechanism underlying the development of a type of essential hypertension.
Hypertension 1987 Nov
PMID:The Milan hypertensive rat as a model for studying cation transport abnormality in genetic hypertension. 331 5

Erythrocyte membrane 22Na and 45Ca transport, osmotic stability and antigenic composition were investigated in 3 strains of rats with spontaneous hereditary hypertension (SHR, SHR SP, MHS), as well as normotensive controls for SHR and SHR SP (WKY) and for MHS (MHS). All strains of spontaneously hypertensive rats showed increased passive membrane permeability for sodium, that was due to increased operation rate of the Na+, K+-cotransport system. Metabolizing sodium is increased in the erythrocytes of Japanese rats (SHR and SHR SP), and decreased in Milan rats (MHS), as compared to normotensive controls. After four hours of incubation with orthovanadate, erythrocyte 45Ca levels were 2-3 times as high in SHR and SHR SP as they were in WKY. In the presence of valinomycin, erythrocyte resistance to hypoosmotic hemolysis was essentially higher in SHR and SHR SP than it was in WKY. These differences are related to a changed rate of anion transport through the band 3 protein. There were no differences in this respect between MHS and MNS. An antigen with a molecular weight of 37-39 kD was detected in erythrocyte membranes of WKY and could not be detected in erythrocytes of other rat groups, including the MNS. It is suggested that different molecular origins of membrane disorders may be an immediate cause of different mechanisms of arterial hypertension in Japanese and Milan animals.
 ...
PMID:[Characteristics of the structural-functional status of erythrocyte membranes in 3 strains of rats with spontaneous genetic hypertension]. 335 98

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 hypertension. 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) F1 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 less than 0.02) and intracellular Na+ content (p less than 0.05) and cell volume (p less than 0.02) were decreased in MHS. The same pattern was observed when this experiment was repeated in different groups of F1 hybrids. In individuals of the segregating F2 population, obtained by crossing the (MHS X MNS) F1 hybrids, there was a positive correlation (p less than 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
PMID:Red blood cell abnormalities and spontaneous hypertension in the rat. A genetically determined link. 388 35

Net fluxes of sodium and potassium ions were determined in sodium-loaded, potassium-depleted erythrocytes from 370 white subjects, 194 of whom had essential hypertension or had been born to parents with essential hypertension. Findings were compared with those in 86 controls who were normotensive and did not have a family history of hypertension. Compared with controls all patients with essential hypertension had a low sodium to potassium ratio secondary to a deficit in the sodium-potassium cotransport system. A similar abnormality was found in subjects born to parents with essential hypertension, the prevalences of a deficient cotransport system in such subjects being 53.6% (52 out of 97) among those with one hypertensive parent and 73.7% (14 out of 19) among those with two hypertensive parents. Both sexes were equally affected. Studies in 14 families over two or three generations showed the erythrocyte cation abnormality in one or more members of each consecutive generation. No close association was evident between the deficient erythrocyte sodium-potassium cotransport system and either blood groups ABO, Rh, Kidd, Duffy, P, and MNS or the major histocompatibility HLA antigens. Out of 90 consecutive unrelated and normotensive white blood donors, 36 showed a low erythrocyte sodium-potassium net flux ratio. It is concluded that in white people abnormal erythrocyte cation transport is a biochemical disorder characteristic of essential hypertension and transmitted by a dominant and autosomal mode expressing a single abnormal gene.
 ...
PMID:Inheritance of abnormal erythrocyte cation transport in essential hypertension. 678 58

Ouabain-like factor (OLF) has been extracted from hypothalamus and adrenal glands of the ox and rats of the Milan hypertensive strain (MHS) and their normotensive controls (MNS). OLF was identified by its ability (a) to inhibit ouabain-sensitive 86Rb uptake into human erythrocytes, (b) to displace [3H]ouabain binding, and (c) to inhibit purified dog kidney Na-K-ATPase. Rat and bovine OLF have similar characteristics. Those that are close to ouabain are (a) ligand conditions for maximal inhibitory activity, (b) high-performance liquid chromatography retention time, (c) reversibility of inhibitory activity on Na-K-ATPase, (d) reduced Na-K-pump inhibitory activity by K+, (e) high affinity for Na-K-ATPase, and (f) no activity on Ca(2+)-ATPase. OLF does not resemble ouabain because the capacity of OLF to inhibit ouabain low-affinity Na-K-ATPase isoform is greater than that of ouabain. The yield of OLF is greater from MHS than MNS hypothalamic and adrenal extracts. These findings represent the first direct evidence that a higher amount of OLF is present in tissues from genetically hypertensive rats than from their inbred normotensive controls, maintained under the same dietary and environmental conditions. This further supports previous observations on the role of OLF in the pathogenesis of MHS hypertension.
 ...
PMID:Characteristics of a ouabain-like factor from Milan hypertensive rats. 750 36

The Milan hypertensive strain (MHS) of rats, in addition to having hypertension, is also characterized by a genetic deficiency in calpastatin, the endogenous inhibitor of calpain. Since this protease has been implicated in long-term potentiation (LTP), we have investigated whether induction of this form of plasticity was altered in this strain of rats as compared to control animals (Milan normotensive strain, MNS). Progressive induction of LTP by increasing numbers of high frequency trains resulted in a greater degree of potentiation measured with all inducing protocols in MHS as compared with MNS animals. This difference was not related to the hypertension, since another hypertensive strain (the SHR strain) and a segregated Milan hypertensive strain, expressing only the hypertension but not the calpastatin deficiency (the MHNE strain), exhibited an LTP indistinguishable from control rats. Treatment of MHNE rats for 2 months with isovalerylcarnitine, a compound that increases calpain activity, also resulted in a greater amount of LTP induced by high frequency trains. These effects were not related to an enhancement of the NMDA receptor dependent component of responses to burst stimulation. These results are consistent with the idea that conditions under which calpain activation is facilitated are associated with a greater degree of synaptic potentiation.
 ...
PMID:A genetic deficiency in calpastatin and isovalerylcarnitine treatment is associated with enhanced hippocampal long-term potentiation. 770 42

The parathyroid hypertensive factor (PHF) is present in the plasma of SHR rats. The authors of this study set out to determine whether this factor was also present in the Lyon (LH male and female) and Milan (MHS male) hypertensive rats. Five week old normotensive rats (LN and MNS) were transplanted with the parathyroid glands of LH and MHS rats immediately after parathyroidectomy (PTX). Plasma calcium fell rapidly after PTX but returned to physiological levels, confirming the functional activity of the graft. Systolic blood pressures of transplanted rats were significantly higher than normotensive LN and MNS controls. These results confirm the role of the parathyroid glands in the genesis of hypertension in Lyon and Milan male and female rats. They suggest that PHF may be implicated in the hypertensive mechanisms of these two models of genetic hypertension.
 ...
PMID:[Genetic hypertension in the rat is partially dependent of parathyroid glands. Results of a crossed transplantation trial]. 812 28

1. High blood pressure is a complex phenotype that involves many body control systems operating at each level of the biological organization. 2. One possible approach to try to identify the major genes involved in the development of hypertension is to dissect the sequence of events that go from a primary protein abnormality that is responsible for organ and cellular dysfunction to arterial hypertension and, then, to go back to the gene coding the protein of interest. 3. Using this approach, our group has been able to identify a candidate protein, adducin, and two point mutations within the two genes coding for the subunits of this protein that are involved in blood pressure variation both in an animal model of primary hypertension and in essential hypertension patients. 4. In the present paper we review the results obtained in the Milan hypertensive rat strain (MHS) and in its appropriate normotensive controls (MNS) to define, at each level of the biological organization, the intermediate phenotypes associated with the development of hypertension. 5. We also demonstrate that this model has many similarities with human hypertension and, in particular, that the same genetic mechanisms linked to a mutation in the adducin gene can explain some of the blood pressure variation in both rats and, at least, in a subgroup of patients. 6. This portion of the increase in blood pressure seems to be able to be selectively inhibited by compounds that interfere with the sequence of events that are triggered by the adducin gene abnormality.
 ...
PMID:A genetic approach to the pathogenesis of primary hypertension and to its treatment. 884 4

The present experiments were concerned with the examination of the hypothesis that a deficiency in calpastatin, the endogenous inhibitor of calpain, enhances learning and memory performance. In the first experiment we used rats with an altered calpain/calpastatin balance (Milan hypertensive strain, MHS, low calpastatin) to investigate the learning and memory of a spatial task in the Morris water maze in comparison with control rats with a normal calpain/calpastatin balance (Milan normotensive strain, MNS). Since the two strains also differ in blood pressure, a third strain of rats was included to assess the role of hypertension (spontaneously hypertensive rats, SHR). Although the acquisition rate of the spatial task was better in the low-calpastatin MHS rats than in their normal-calpastatin MNS controls, their performance was similar to that of the SHR rats, thus thwarting the conclusion that differences were due to the low level of calpastatin. The availability of another mutant strain, low-calpastatin level and normotensive (MH.NE), allowed a further examination of the hypothesis. In the second experiment rats of the MH.NE strain acquired the spatial task as well as their normotensive controls, but their memory retrieval was clearly less than that of their normal-calpastatin controls. This deficiency was not due to impaired visual function or a slower swimming speed. The conclusion is that an inbalanced calpain/calpastatin ratio, although favoring calpain activity, is disadvantageous for remembering a spatial task. This disadvantage is clearly overruled when this inbalance is accompanied by hypertension.
 ...
PMID:Spatial learning and memory in calpastatin-deficient rats. 894 15


<< Previous 1 2 3 Next >>