Coexisting independent sodium-sensitive and sodium-insensitive mechanisms of genetic hypertension in spontaneously hypertensive rats (SHR)

2001 ◽  
Vol 79 (9) ◽  
pp. 779-784 ◽  
Author(s):  
Ibert C Wells ◽  
Alan J Blotcky
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Plasma Membranes ◽  
The Other ◽  
Erythrocyte Membranes ◽  
Hypertensive Rats ◽  
Rat Strains ◽  
Spontaneously Hypertensive ◽  
Enhanced Diffusion ◽  
Enzyme Systems ◽  
Intracellular Ca

Some essential hypertensive patients and genetic hypertensive rat strains have less than the normal levels of Mg2+ tightly bound to the plasma membranes of their erythrocytes and other cells, i.e., the magnesium binding defect (MgBD). This binding defect appears to cause increased passive permeability of the membrane to Na+ and thereby its increased intracellular concentration, particularly if the Na+-extrusion enzyme systems of the cell are also defective. The Na+-Ca2+ exchange system in the cell membrane exports Na+ and imports Ca2+, increasing the tone of the smooth muscle cell and thus producing hypertension (HTn). This HTn is Na+-sensitive. Evidence supporting this postulate was obtained by determining the intraerythrocyte total concentrations of Na+, Ca2+, K+, and Mg2+ in two strains of spontaneously hypertensive rats (SHR and SS/Jr rats, having the MgBD together with the other requisites of the Na+-sensitive pathway) and their respective controls (WKY and SR/Jr rats, in which this complete pathway is absent). The Na+ and Ca2+ concentrations in the hypertensive rats were increased, and that of K+ was decreased. The concentrations of these cations were very similar in the two hypertensive strains. The level of membrane tightly bound Ca2+ in SHR erythrocyte membranes was significantly higher than those in the other three rat strains, which were not statistically different from each other. These results support previously reported evidence of the existence of a novel HTn-generating mechanism in the SHR rat, in which the intracellular Ca2+ concentration is increased as the result of the enhanced diffusion of this ion into the cell and the accompanying deficiency of the Ca2+ extrusion enzyme systems. This pathway is therefore Na+-insensitive, i.e., Ca2+-sensitive.Key words: essential hypertension, Na+-sensitive hypertension, Na+-insensitive hypertension, Ca2+-sensitive hypertension.

Two new inbred rat strains derived from SHR: WKHA, hyperactive, and WKHT, hypertensive, rats

1991 ◽  
Vol 261 (2) ◽  
pp. H583-H589 ◽  
Author(s):  
E. D. Hendley ◽  
W. G. Ohlsson
Keyword(s):  
The Other ◽  
Hypertensive Rats ◽  
Rat Strains ◽  
Spontaneously Hypertensive ◽  
Behavioral Profile ◽  
Behavioral Abnormalities ◽  
Inbred Rats ◽  
Wistar Kyoto ◽  
Inbred Rat ◽  
Biological Differences

Two new strains of inbred rats have been developed. One, WKHA, exhibits hyperactivity, and the other, WKHT, exhibits hypertension. Both of these traits are expressed in the SHR. By crossing spontaneously hypertensive rats (SHRs) with Wistar-Kyoto (WKY) controls, followed by recombinant selected inbreeding, we succeeded in genetically separating the hyperactivity from the hypertension in two new strains. Longitudinal studies indicate a persistence of hypertension without hyperactivity in WKHTs, and hyperactivity without hypertension in WKHAs, over at least 1 year. Ventricular enlargement, another characteristic of SHRs, was observed in adult WKHTs after the onset of hypertension; however, ventricles were already enlarged in normotensive WKHAs at 6 wk. The emergent behavioral profile of WKHAs indicates that they retain the hyperactivity trait and hyperreactivity to stress, and not some of the other behaviors of SHRs, such as poor habituation. Studies in WKHTs suggest that they are an improvement over SHRs as a model of genetic hypertension as they lack some prominent behavioral abnormalities. Nevertheless, the four genetically related strains (WKHA, WKHT, SHR, and WKY), used together, are considered most appropriate for seeking correlations of biological differences with either hypertension or hyperactivity.

Further analysis of cell membrane changes in genetic hypertension in rats by diphenylhexatriene fluorescence polarization

1984 ◽  
Vol 66 (6) ◽  
pp. 717-723 ◽  
Author(s):  
I. Aracon-Birlouez ◽  
T. Montenay-Carestier ◽  
M. A. Devynck
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Erythrocyte Membranes ◽  
Shr Rats ◽  
Erythrocyte Ghosts ◽  
Hypertensive Rats ◽  
Salt Loading ◽  
Spontaneously Hypertensive ◽  
Platelet Membranes ◽  
Wistar Kyoto ◽  
Membrane Changes

1. Fluorescence Dolarization of dbhenvlhexa-triene embedded in membranes was used as an index of ‘microviscosity’ in platelets and ervthro—cyte ghosts of spontaneously hypertensive rats of the Okamoto-Aoki strain (SHR), Wistar-Kyoto strain (WKY) and of the hypertension-prone and -resistant Sabra strains (SBH and SBN), and the original Sabra strain (SB). 2. Microviscosity was increased both in erythrocyte ghosts and platelet membranes of male but not female SHR rats compared with WKY rats and in hypertension-prone Sabra rats compared with the original Sabra rats. 3. Acute and chronic salt loading increased the microviscosity of platelet membranes in all strains of rats but had no effect on the erythrocyte membranes. 4. Microviscosities of vesicles made of lipids extracted from SHR and WKY erythrocyte ghosts were similar. This supports the hypothesis that membrane proteins play a major role in the differences in microviscosity observed in SHR rats.

Calcium Accumulation and Calcium Binding by the Cell Membranes of Cardiomyocytes and Smooth Muscle of Aorta in Spontaneously Hypertensive Rats

1980 ◽  
Vol 59 (s6) ◽  
pp. 207s-209s ◽  
Author(s):  
S. N. Orlov ◽  
Yu. V. Postnov
Keyword(s):  
Smooth Muscle ◽  
Erythrocyte Membrane ◽  
Calcium Binding ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Membranes ◽  
Hypertensive Rats ◽  
Binding Ability ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Lower Ability

1. The ability of isolated membrane fractions of cardiomyocytes, aortic smooth muscle and erythrocytes from spontaneously hypertensive rats to bind calcium was investigated isotopically. 2. Plasma membranes of aortic smooth muscle and erythrocytes of spontaneously hypertensive rats possess a lower calcium-binding ability than preparations from normotensive controls. 3. Sarcoplasmic reticulum from the myocardium of spontaneously hypertensive rats had a lower ability to accumulate calcium. 4. Changes in the calcium-binding ability of the erythrocyte membrane of spontaneously hypertensive rats was related to the diminution of the amount of exchangeable calcium on the inner part of the membrane. The latter may be the cause of the increase of erythrocyte membrane permeability for sodium in spontaneously hypertensive rats and in patients with essential hypertension.

Isoflurane Alters Angiotensin II–Induced Ca2+Mobilization in Aortic Smooth Muscle Cells from Hypertensive Rats

2002 ◽  
Vol 97 (3) ◽  
pp. 642-651 ◽  
Author(s):  
Emmanuel Samain ◽  
Hélène Bouillier ◽  
Catherine Rucker-Martin ◽  
Jean-Xavier Mazoit ◽  
Jean Marty ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Smooth Muscle Cell ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Intracellular Ca ◽  
Wistar Kyoto

Background Angiotensin II (AngII) is a potent vasoconstrictor involved in the short-term control of arterial blood pressure. Isoflurane was reported to decrease vascular tone through an alteration of vascular smooth muscle cell vasomotor response to several agonists, but its effect on AngII signaling is not known. On the other hand, vascular response to AngII is altered in hypertension. In this study, the authors tested the hypothesis that (1) isoflurane alters AngII-induced intracellular Ca mobilization in aortic vascular smooth muscle cell from Wistar Kyoto and spontaneously hypertensive rats, and (2) this effect could be associated with an alteration of the organization of microtubular network, reported to be involved in AngII signaling. Methods The effect of 0.5-3% isoflurane was studied (1) on AngII (10 m)-induced intracellular Ca mobilization, intracellular Ca release from internal stores, and Ca influx in Fura-2 loaded cultured aortic vascular smooth muscle cell isolated from 6-week-old Wistar Kyoto and spontaneously hypertensive rats, using fluorescent imaging microscopy; and (2) on the organization of cytoskeletal elements, using immunofluorescence labeling. Results In both stains, isoflurane decreased in a concentration-dependent manner AngII-induced intracellular Ca mobilization, Ca release from internal stores, and Ca influx through nifedipine-insensitive Ca channels. This effect occurred at a lower concentrations of isoflurane in Wistar Kyoto rats than in spontaneously hypertensive rats. In both strains, the effect of isoflurane on AngII- Ca mobilization was abolished by impairment with nocodazole, vinblastine, or paclitaxel of microtubules polymerization. Isoflurane directly altered tubular network organization in a concentration-dependent and reversible manner. Conclusions Isoflurane decreased AngII-induced Ca mobilization at clinically relevant concentrations, suggesting that vascular response to AngII could be altered during isoflurane anesthesia. The hypertensive strain was found less sensitive than the normotensive one. In both strains, the isoflurane effect was associated with a microtubular network interaction.

Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats

2000 ◽  
Vol 278 (1) ◽  
pp. L81-L89 ◽  
Author(s):  
Rajamma Mathew ◽  
Newton Y.-T. Fan ◽  
Ning Yuan ◽  
Praveen N. Chander ◽  
Michael H. Gewitz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Pulmonary Arteries ◽  
The Other ◽  
Pulmonary Vasculature ◽  
Vascular Changes ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Medial Wall Thickness

To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N ω-nitro-l-arginine (l-NNA; 15 mg ⋅ kg−1 ⋅ day−1orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. l-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 ± 2 vs. 19 ± 1%).l-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 ± 7 vs. 88 ± 4% for WKY) was associated with an increase in WT (37 ± 1%) and RV/BW (0.76 ± 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.

Role of receptor elements in baroceptor resetting

1979 ◽  
Vol 236 (1) ◽  
pp. H174-H182 ◽  
Author(s):  
H. N. Sapru ◽  
A. J. Krieger
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Wistar Rats ◽  
Antihypertensive Agents ◽  
Vascular Wall ◽  
The Other ◽  
Threshold Pressure ◽  
Hypertensive Rats ◽  
Nerve Activity ◽  
Spontaneously Hypertensive

Spontaneously hypertensive rats (SHR), 4 wk of age, were treated with antihypertensive agents for 40 wk. The treatment was withdrawn for 2 wk so that the animals experienced hypertension for about 1 wk. The aortic arch was then perfused and aortic nerve activity was recorded. The threshold pressure was 140 mmHg in these SHR. This threshold pressure was less than that observed in age-matched untreated SHR (160--180 mmHg) but greater than that observed in age-matched Kyoto-Wistar rats (80--120 mmHg), indicating partial baroceptor resetting. No significant changes were observed in the vascular wall in these SHR, and partial baroceptor resetting was completely reversed when short duration of hypertension was reversed. On the other hand, baroceptor resetting in untreated SHR was always accompanied by significant changes in vascular wall, and reversal of baroceptor resetting was contingent upon regression of vascular wall hypertrophy. Partial baroceptor resetting in absence of significant changes in vascular wall may be explained by adaptation of baroceptors to persistent high blood pressure.

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