Spontaneously Hypertensive Strains Research Articles

Diferencias fenotípicas ante la devaluación y omisión de una recompensa esperada

La frustración es una respuesta comportamental, emocional y neurobiológica concomitante a la discrepancia negativa entre el refuerzo esperado y el obtenido, ya sea por la devaluación u omisión del incentivo. Los modelos animales y la comparación de cepas endocriadas han permitido estudiar la contribución de los factores genéticos a la expresión de diferencias fenotípicas en tales situaciones. El objetivo consistió en comparar cepas que difieren en su comportamiento emocional ante la devaluación (Exp 1) y omisión (Exp 2) de un refuerzo: las ratas espontáneamente hipertensas (SHR) y normotensas Wistar Kyoto (WKY). En ambos experimentos se halló que las SHR realizaron significativamente más respuestas de ingesta durante la fase de adquisición. En la fase de prueba del Exp 1, se observó una recuperación enlentecida de su respuesta. En el Exp 2 no se observaron diferencias entre cepas. La cepa emocionalmente más reactiva (SHR) no difirió con respecto a su control (WKY) en la reacción inicial ante la devaluación del refuerzo, pero mostró una recuperación enlentecida. Estos datos son congruentes con la literatura que sugiere que, ante la devaluación del incentivo, las diferencias fenotípicas se expresan con mayor facilidad en la recuperación de la respuesta (frustración secundaria).

Intermittent Functioning of Baroreflex Contributes to the Etiology of Hypertension in Spontaneously Hypertensive Rats

The potential roles of the baroreflex in long‐term arterial blood pressure (BP) regulation and in the etiology of primary hypertension have been long debated. We have hypothesized that aging‐associated stiffening of large arteries desensitizes baroreceptors in the aortic arch and carotid sinus, and thereby may contribute to a mechano/neurogenic etiology. To test that hypothesis, we obtained long time‐course continuous arterial pressure data in spontaneously hypertensive (SHR) and control Wistar‐Kyoto (WKY) rats at various ages (7–15 weeks) during the development of the hypertensive phenotype in the SHR animals. Rather than the expected simple proportional relationship between arterial vessel distensibility and baroreflex gain, analysis of data from these animals reveals a markedly intermittent functioning of the baroreflex arc, with long periods (up to several minutes long) with arterial pressure fluctuations coupled to corresponding physiological responses in heart rate and with similarly long periods where the pressure and heart rate fluctuations are not coupled. Several potentially important trends are observed to be associated with the intermittent apparent baroreflex “on” and “off” time periods: (1.) during normal dark‐cycle recording the fraction of time for which the baroreflex is operating in the “on” state ranges from 45–70% for both strains and all ages observed; (2.) the fraction of time in the “on” state decreases with age in both the SHR and WKY strains; (3.) the mean arterial pressure is tightly correlated with fractional “on” time in all rats (see figure ); (4.) mean pressures during “off” states are higher than during “on” states for both strains, both sexes, and at all ages studied; and (5.) mean pressure tends to decrease during “on” states and rise during “off” states in WKY rats, while mean pressure remains elevated at all times in SHR rats. From these observations we hypothesize that impaired function of the baroreflex in the SHR strain contributes to the SHR hypertensive phenotype. This impaired function is reflected in less frequently coupled “on” function in the SHR compared to the WKY and the inability of the functioning baroreflex to reduce pressure during “on” states in the SHR.Support or Funding InformationSupported by NIH grant HL139813Correlation between mean arterial pressure and fractional baroreflex “on” time in SHR and WKY rats.Figure 1

Impact of genetic strain on body fat loss, food consumption, metabolism, ventilation, and motor activity in free running female rats

Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65days compared to sedentary (SED) housing in five female rat strains: Sprague–Dawley (SD), Long–Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise.

Secondary Histomorphological Changes in Cerebral Arteries of Normotensive and Hypertensive Rats following a Carotid-Jugular Fistula Induction

Haemodynamic changes in cerebral circulation are associated with the natural ageing process and associated pathology, leading to the development of incapacitating neurological and neurovascular diseases. Due to inherent biological limitations, current literatures mostly aimed at studying the correlation descriptively or quantifying the relationship in vitro or using computational models. In this paper, a model of a carotid-jugular fistula in the rat was used to create a haemodynamic insult to the intracranial arterial circulation and subsequent venous drainage. An arterial-venous (AV) fistula was created in 12 rats, 6 of which are normotensive Wistar-Kyoto strain (WKY) and the rest spontaneously hypertensive strain (SHR) with an additional 6 in each strains designed as controls without previous surgery. After 4 weeks of convalescence, all 24 rats were euthanised and their cerebral circulation was examined histomorphologically. We confirmed an intrinsic morphological difference between normotensive WKY and hypertensive SHR and found a modest but significant arterial shrinkage in both strains induced with AV fistula. We also reported that alterations in blood flow are also associated with marked extracellular matrix changes. We concluded that the model was suitable for studying the relative contributions of altering haemodynamic patterns and venous drainage on cerebrovascular changes. We also found that hypertension modulated cerebral vascular changes in addition to disrupted blood flow.

Atypical Ca2+ currents in chromaffin cells from SHR and WKY rat strains result from the deficient expression of a splice variant of the α1D Ca2+ channel

Ca(2+) currents (I(Ca)) recorded from adrenal chromaffin cells (CCs) of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats are similar to one another, but different from those recorded in other rodent species. I(Ca) in WKY/SHR CCs comprises an early, transient (I(Ca(e))) and a late, sustained component (I(Ca(s))). In Wistar CCs, I(Ca(e)) is absent, and I(Ca(s)) is of greater amplitude. Activation and steady-state inactivation of I(Ca(e)) and I(Ca(s)) in WKY/SHR CCs suggest the recruitment of at least two populations of Ca(2+) channels with different voltage dependence and kinetics. In WKY/SHR CCs, I(Ca(e)) is inhibited by nifedipine, enhanced by BAY K 8644, is not blocked by the mibefradil analog NNC 55-0396, and displays Ca(2+)-dependent inactivation and fast deactivation kinetics, suggesting that it results from the opening of L-type rather than T-type Ca(2+) channels. I(Ca(e)) properties suggest that it originates from the opening of Ca(2+) channels formed with the short splice variant (Ca(V)1.3(42A)). RT-PCR showed that expression of Ca(V)1.3(42A) mRNA is similar in both Wistar and WKY/SHR, but that the long variant (Ca(V)1.3(42)) is virtually absent in WKY/SHR. Thus I(Ca(e)) corresponds to the recruitment of Ca(V)1.3(42A) channels, unmasked by the absence of Ca(V)1.3(42) channels. Studies in WKY CCs do not report major functional alterations, despite the unusual expression pattern of Ca(V)1.3 splice variants. It remains to be established if more subtle functional alterations exist, and if the atypical splicing pattern of Ca(V)1.3 could be related to the functional and behavioral alterations reported in WKY/SHR rats, including their susceptibility to develop hypertension.

Nitric oxide synthase distribution in the rat spinotrapezius muscle related to hypertension

There are gaps in the fundamental understanding of the expression of nitric oxide synthases (NOS) in the microvasculature. We examined localization of NOS1 (nNOS), NOS2 (iNOS) and NOS3 (eNOS) in the spinotrapezius muscle of 8‐week old male Wistar‐Kyoto (WKY) and Spontaneously Hypertensive (SHR) rats using immunohistochemistry and brightfield microscopy. Muscles were removed and frozen in liquid N2‐chilled isopentane. Ten μm cross‐sections were cut and incubated with antibodies to NOS1, NOS2 and NOS3 and visualized using a proprietary avidin: biotinylated enzyme complex and 3,3'‐diaminobenzidine. Image analysis demonstrated 33.6% less NOS1 and 52.3% less NOS3 in the WKY vs. SHR. NOS2 expression was 72.5‐fold (7150%) greater in the WKY vs. the SHR. However, NOS2 expression in the WKY was 37.9% less than NOS1 expression and 36.3% less than NOS3 expression, compared to 98.7% and 98.2% in the SHR. Although our NOS2 expression results are surprising, previous studies have provided conflicting data regarding differences in NOS expression between WKY and SHR strains. Continued study should provide a more accurate understanding of differences in NOS expression between these two strains of rats. Support: Grants HL18292 and HL079087 from NHLBI

Estudo do efeito da amiodarona sobre o peso corpóreo e sobre determinantes morfológicos e citopatológicos do pulmão em ratos machos e fêmeas das linhagens Wistar, Wistar-Kyoto e SHR

Introdução: A maioria dos estudos experimentais sobre a toxicidade pulmonar induzida por amiodarona tem sido realizada em ratos machos da linhagem Fischer-344. Objetivos: Investigar o efeito da amiodarona sobre o peso corpóreo e sobre determinantes morfológicos e citopatológicos do pulmão em outras linhagens de ratos de ambos os sexos. Métodos: Grupos de ratos machos e de fêmeas das linhagens Wistar, Wistar-Kyoto (WKY) e espontaneamente hipertenso (SHR) receberam, por gavagem, durante quatro semanas, 175mg/kg/dia de amiodarona em suspensão salina. Os grupos controles receberam apenas salina. Foram estudados ganho de peso corpóreo, celularidade total e diferencial do lavado broncoalveolar (LBA) e histopatologia dos pulmões. Resultados: Mortalidade pela amiodarona foi observada nos ratos WKY tratados, sendo maior em machos. Animais SHR tratados de ambos os sexos apresentaram o menor ganho de peso entre as linhagens estudadas. Ratos machos Wistar e SHR tratados apresentaram maior ganho de peso do que as fêmeas das suas respectivas linhagens. O LBA de ratos SHR tratados de ambos os sexos era hemorrágico. A celularidade do LBA foi maior em machos tratados (WKY > Wistar > SHR). Entretanto, nos machos e fêmeas WKY a contagem diferencial mostrou o menor percentual de macrófagos e o maior de neutrófilos entre as três linhagens. Macrófagos do LBA de ratos Wistar tratados apresentavam fosfolipidose, enquanto a maioria dos macrófagos de ratos SHR tratados eram normais. No exame anatomopatológico dos pulmões, não houve diferenças entre os sexos e não foi observada pneumonite. Em ratos Wistar o exame foi caracterizado pela acentuada quantidade de macrófagos "espumosos" intra-alveolares, em ratos WKY, por inúmeros abscessos intraparenquimatosos e em ratos SHR, pela hemorragia alveolar. Conclusões: 1) a amiodarona induz em ratos Wistar maior quantidade de macrófagos espumosos do que nas linhagens WKY e SHR, embora no modelo utilizado eles não desenvolvam pneumonite; 2) a amiodarona tem maior efeito sobre os determinantes morfológicos e citopatológicos do pulmão em animais do sexo masculino.

Uptake and release of Ca2+ in chemically skinned aortic strips from spontaneously hypertensive (SHR) and normotensive (WKY) rats.

The uptake and release of Ca2+ were studied in EGTA-skinned aortic strips from spontaneously hypertensive rats (SHR strain: SAP = 191 +/- 5 mmHg, n = 27) and normotensive control rats (WKY strain: SAP = 131 +/- 2 mmHg, n = 25). 45Ca uptake was measured as a function of time (0.5 to 30 min.), at pCa 6.6, in the presence of 10 mM of K oxalate. Skinned aortic strips of SHRs accumulated more Ca2+ after 30 min of uptake than those of WKY rats (0.66 +/- 0.05 vs 0.52 +/- 0.03 nmole.mg-1 wet tissue; p < 0.05). A lower activity of the transport system in the hypertensive group was evidenced by the fraction of these maximal uptake values accumulated after 2 minutes of uptake, 56% compared with 98% in the normotensive group. 45Ca release was assayed in skinned aortic strips preloaded for 30 minutes with 45Ca in the absence of K oxalate and desaturated with washing solutions containing 3 nM free Ca2+. 30 mM of caffeine, 5 microM of norepinephrine or 10 microM of IP3 resulted in greater increases in the rates of Ca2+ efflux in WKY than in SHR aortic strips. Net effluxes of Ca2+ upon stimulation with all these drugs were statistically significant only in the hypertensive group due to its slightly but consistently higher Ca2+ content. Changes in both rate of efflux and net efflux induced by 30 mM of caffeine could be blocked by 0.6 mM of ryanodine. The sarcoplasmic reticulum is characterized in the genetically hypertensive rats by a low transport activity of its Ca(2+)-ATPase, a high Ca2+ content and a Ca2+ release mechanism with low responsiveness to stimulation by caffeine, norepinephrine and IP3.

Relationship of growth and blood pressure in inbred rats.

Blood pressure and body weight rise with age, and hypertension is hypothesized to result from an early disorder of growth. We used the statistical technique of spline fitting to examine patterns of growth and rising blood pressure in individual inbred rats of the Wistar-Kyoto, spontaneously hypertensive (SHR), and stroke-prone SHR strains. Our results indicate that growth is phasic and that a well-defined growth spurt peaks at approximately 50 days of age in each strain. In addition, the time of maximal weight gain corresponds to the onset of a blood pressure spurt. The timing of this blood pressure rise was similar in the three strains, but the maximal rate of blood pressure rise was significantly higher in the hypertensive strains. Our results suggest that growth and rising blood pressure are intimately linked. Blood pressure appears to rise in response to a growth spurt, suggesting that there are growth-related events that trigger the cardiovascular response.

Angiotensin II binding in area postrema and nucleus tractus solitarius of SHR and WKY rats

The distribution of angiotensin II (AII) binding sites in the area postrema (AP) and adjacent nucleus tractus solitarius (NTS) was compared in spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. 125[Saralasin 1-Isoleucine 8]-Angiotensin II ( 125I[SI]-AII) binding density was quantitated from autoradiographic images by computer-assisted image analysis. Seventeen 30 μm serial coronal sections inclusive of the entire AP were analyzed as either individual sections or as groups of sections designated as caudal, middle, or rostral area postrema regions. 125I[SI]-AII binding density was greatest in caudal AP and declined progressively in the rostral direction in both strains; however, binding density in SHR was significantly higher than in WKY rats at each level of the AP analyzed. 125I[SI]-AII binding in the entire area postrema was approximately 46% higher in SHR rats. In the NTS, however, there were no differences in binding density between strains. At the middle level of the AP, 125I[SI]-AII binding was highest in the ventral midline and lowest in the dorsolateral region. In the NTS, the highest 125I[SI]-AII binding density was found in the pars commissuralis and pars medialis. In conclusion 1. a) 125I[SI]-AII binding density was nonhomogeneus in the AP and NTS of both strains, 2. b) qualitatively similar patterns of nonhomogeneity of binding in the AP and NTS were noted in both strains; however, 3. c) the SHR strain consistently had higher density AII binding than WKY in AP, but not in NTS.

Sex differences in physical dependence on pentobarbital in four inbred strains of rats

1. 1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, pentobarbital (PB)-induced sleep time was much longer in female than in male rats. 2. 2. At the time of awakening, brain levels of PB were significantly higher in the female F344 than in the male rats, but there was no sex differences in other strains. 3. 3. Each strain of rats was treated with PB-admixed food for 47 days. There were significant sex differences in mean drug intake of the SHR and LEW strains, but not the WKY and F344 strains during the final concentration. 4. 4. Only female rats exhibited moderate to severe motor impairment by PB. 5. 5. After PB treatment ended, various signs of PB withdrawal occurred in female, but not male, rats. These marked sex differences were observed in all four inbred strains. 6. 6. The sex differences in physical dependence on PB may be due mainly to differences in rates of drug metabolism for the LEW, SHR and WKY rats, and to differences in CNS sensitivity for the F344 rats.

Radial immunodiffusion assay for rat α1-acid glycoprotein

α 1-Acid glycoprotein (AGP) is an “acute phase protein” whose expression is altered in several human pathologies. Using antiserum from New Zealand white rabbits, a radial immunodiffusion assay for measuring AGP levels in rat plasma was developed operating in the range of 50–2500 μg/ml with high specificity. Standard curves were constructed (precipitin ring diameter 2 vs. μg/ml AGP) yielding highly linear plots (r=.98). The plasma concentration of AGP in spontaneously hypertensive (SHR) rats was double that of the normotensive Kyoto-Wistar (WKY) rats (208±10 vs. 118±5 μg/ml). AGP induction by turpentine resulted in a 14- and 26-fold increase in AGP levels in SHR and WKY rats, respectively. Induction of AGP by dexamethasone injection was examined in the SHR and WKY rat strains resulting in a 5- and 12-fold increase in AGP levels, respectively. AGP concentration in whole brain of rats was determined to be 12.7 ± 1.8 μg/g. AGP concentrations in SHR and WKY liver were also determined to be 159 ± 3 and148 ± 5 μg/g liver tissue.

Fatty Acid Composition of Milk from Genetically Normotensive and Hypertensive Rats

To assess milk fatty acid composition in genetically normotensive (Wistar Kyoto, WKY) and spontaneously hypertensive (SH) rats, WKY and SH dams (n = 10/strain) were milked under halothane anesthesia on d 5, 13 and 21 postpartum. Milk samples of 0.5-1.0 mL were then analyzed by gas-liquid chromatography. Additional WKY and SH dams (n = 2/strain) were milked on d 5 and 21 postpartum for assessment of total milk fat. In both WKY and SH strains, the amount of 8:0 and 10:0 fatty acids increased from d 5 to 21 (p less than 0.001), whereas the quantity of 18:3(n-6), 20:3(n-9), 20:3(n-6), 22:4(n-6), 22:5(n-3) and 22:6(n-3) fatty acids declined over the same period (p less than 0.001). Milk from SH rats had higher levels of 10:0 and 20:4(n-6) fatty acids on all sampling days than did milk from WKY rats (p less than 0.001), and milk from SH rats had lower levels of 16:1(n-7), 18:1(n-9) and 18:2(n-6) fatty acids on d 13 and 21 (p less than 0.001). There were no differences in milk fat content between strains. These data suggest that genetically hypertensive rat pups obtain significantly greater amounts of 20:4(n-6) and significantly lower amounts of 18:2(n-6) fatty acids from maternal milk than do their normotensive counterparts.

Strain differences in central nervous system concentrations of cholecystokinin between normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats

The regional brain and spinal cord concentrations of cholecystokinin-octapeptide (CCK-8) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of CCK-8 in the WKY strain was hippocampus (20.5 ± 1.3 pmol/g) > cortex > striatum = hypothalamus > midbrain = thalamus > spinal cord > medulla oblongata/pons ( MO P , 1.6 ± 0.2 pmol/g) whereas in the SH strain this order was hippocampus (12.9 ± 0.8 pmol/g) > cortex = striatum > hypothalamus > midbrain > thalamus = spinal cord > MO P (1.4 ± 0.2 pmol/g). The concentrations of CCK-8 in the cerebellum were at the level of assay sensitivity (0.5 pmol/g in both strains). In comparison to the WKY rats, the SH strain had significantly lower levels of CCK-8 in the hippocampus (−37%), cortex (−28%), spinal cord (−23%) and pituitary (−57%). The lowered levels of CCK-8 in the brain of the SH rat may be causally related to, or result from, the cardiovascular, behavioural or morphological abnormalities of this strain.

Cardiac membrane vitamin E and malondialdehyde levels in heart muscle of normotensive and spontaneously-hypertensive rats.

The vitamin E (alpha-tocopherol) and free and bound malondialdehyde (MDA) in ventricular heart muscle and myocardial membrane from Wistar-Kyoto (W/K) normotensive and spontaneously hypertensive (SH) rats have been measured directly by high performance liquid chromatography (HPLC). Thiobarbituric acid-reactive substance (TBA-RS) in the myocardium and heart-muscle membrane of the two strains was also quantified by a colorimetric TBA test. It was found that SH-rat myocardium and myocardial membrane contained more than 3-fold less alpha-tocopherol than did heart muscle and cardiac membrane of the normotensive rat. Coincident with this relative vitamin E deficiency were several-fold greater amounts of MDA and TBA-RS in SH-rat myocardium and myocardial membrane. Most (87%) of the MDA in SH-rat heart muscle, but only 40% in W/K-rat heart muscle, was free (i.e., unbound). These results offer direct evidence that SH-rat myocardium is vitamin E-deficient and highly peroxidative, relative to cardiac muscle of the normotensive W/K parent strain. The lower vitamin E content of SH-rat myocardium is particularly striking, because SH-rat myocardial membrane was found to contain approximately 35% more phospholipid than myocardial membrane in the W/K rat. Although the amounts of myocardial TBA-RS are greater in the SH strain, they do not reflect the actual MDA profiles of the heart muscles or the heart membranes and cannot be used as a quantitative index of cardiac oxidative-injury status due to non-MDA TBA-RS in both strains.

Further evidence for genetic independence of blood pressure and salt appetite in spontaneously hypertensive and Wistar-Kyoto rats.

We previously reported that blood pressure and volitional consumption of salt were under independent genetic regulation in the F2 population of crosses between Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY) rats. However, the use of 1.5% NaCl as the test solution in that study might have resulted in a limit on the range of variability in saline consumption that could possibly have obscured a correlation between these traits, if one existed. In the present study, volitional consumption of normal (.9%) saline and blood pressure were measured in a sample of 61 adult male F2 (SHR x WKY) rats. There was considerable inter-individual variance in saline consumption (2 to 100 ml/day), indicating that the range of intake was not truncated in this experiment. However, there was no correlation between blood pressure and any measure of saline consumption in the F2 sample, again indicating that ad libitum salt appetite and blood pressure are genetically independent in the SHR and WKY strains of rats.

Evaluation of right and left ventricular size in SHR-Wistar hybrids.

The relative right and left ventricular sizes were evaluated in hybrid rats obtained by crossing spontaneously hypertensive (SHR) and pure Wistar strains to detect cardiac hypertrophy dissociated from the hypertension genetically transmitted by the SHR strain. In female hybrids of the the F1, F2, and F3 generations, both ventricles were found to have bigger size in relation to body weight than in the pure Wistar, whereas only the F3 group was hypertensive. All generations of male hybrids had arterial pressure values in the hypertensive range, which were not consistently accompanied by increases in the ventricle mass. The correlation between arterial pressure and indexes of ventricular size was assessed in sex-age matched groups. In a range of systolic pressure values of 100-200 mmHg, the variables showed no correlation or poor positive correlation (correlation coefficient values from -0.3641 to 0.6153). The correlation was not improved in the F3 generation as would be expected, because these hybrids underwent higher left pressure load than the preceding generations. The results indicate that increased ventricular size in SHR-Wistar hybrids may be independent from the hypertension genetically transmitted by the SHR strain and suggest that some of the previously proposed factors, i.e., cardioadrenergic activity or the growth factor isolated from SHR hearts, may be playing a role in the ventricular hypertrophy process in this strain. If this characteristic of hybrids is a constant in pure SHR strain, its validity as a model of cardiac hypertrophy due to left pressure overload would be questioned.

The spontaneously hypertensive rat's preference for salted foods

Sprague-Dawley rats drink mild salt (NaCl) solutions in preference to plain water. In contrast, rats of this strain are less likely to show preferences when salt is tested in food. Others have established that rats of the spontaneously hypertensive strain (SHR) have greater preferences for salt water than do their normotensive counterparts (WKY). The question addressed in the present research was whether SHR rats would show an enhanced salted food preference when compared with WKY rats. SHR and WKY rats were given choices between a variety of salted and unsalted foods. When tested with potato chips, no major strain differences in salt preferences were observed; depending on concentrations, rats ate either equal amounts of salted and unsalted chips or avoided salted chips. However, when tested with liquid milk products (heavy cream and half & half), SHR rats showed both higher salt preferences and consumed more salt. The SHR actually preferred these products salted, whereas the WKY rats, like Sprague-Dawley rats, never ate more salted milk than plain milk. When tested with skim milk, SHR and WKY did not differ; both preferred the milk salted. In order to test the effect of physical state (or texture) upon salt preference, the skim milk was gelled. Salt preferences of the SHR rats fell to 50% whereas the salt preferences of the WKY rats remained unchanged.

Hypertension produced by a high sodium diet in the borderline hypertensive rat (BHR).

The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made. Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension.

Regional brain concentrations of vasoactive intestinal polypeptide in normotensive Wistar-Kyoto and spontaneously hypertensive rats

The regional brain and spinal cord concentrations of vasoactive intestinal polypeptide immunoreactivity (VIP) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of VIP in the WKY strain was cortex (44 pmol/g) > hippocampus = striatum > midbrain = hypothalamus > medulla oblongata/pons = lumbar spinal cord (SC) > cervical SC > thoracics SC (2.5 pmol/g) whereas in the SH strain this order was cortex (35 pmol/g) > striatum = midbrain > hippocampus = hypothalamus > medulla oblongata/pons = lumbar SC > cervical SC > thoracic SC (1 pmol/g). The VIP concentraions of the thalamus, cerebellum and pituitary were at the level of assay sensitivity (0.5 pmol/g) in both strains. In comparison to the WKY, the SH rats had significantly lower VIP levels in the hippocampus (−42%) and cervical (−46%) and thoracic (−56%) spinal cord but significantly higher levels in the midbrain (+64%).