Spontaneously Hypertensive Strains Research Articles

Age-related changes in neuropeptide Y immunoreactivity (NPY-ir) in the cortex and spinal cord of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats.

The concentrations of neuropeptide Y immunoreactivity (NPY-ir) were measured in the cortex and cervical, thoracic and lumbar spinal cord of 8-, 18- and 31-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). This peptide was measured using a highly sensitive and specific radio-immunoassay (RIA) developed in our laboratory. The concentrations of NPY-ir in the cortex, cervical and thoracic spinal cord were significantly different between the two strains, with the levels being consistently lower in the SHR strain independent of age. While there was no obvious change in the levels of NPY-ir in the cortex with increasing age, there was a general trend for the levels to fall in all three spinal cord regions. The rate of decrease of NPY-ir in the thoracic spinal cord appeared greater in the SHR compared with the WKY rats. These biochemical differences observed in the cortex and thoracic spinal cord of SHR and WKY rats may be related to the behavioural and blood pressure differences observed in these strains.

Influence of neonatal handling on blood pressure, locomotor activity, and preweanling heart rate in spontaneously hypertensive and Wistar Kyoto rats.

This experiment tested the hypothesis that increased stimulation early in development would (a) alter developmental changes in heart rate and behavioral reactivity and (b) affect the level at which blood pressure was regulated in adulthood. For this purpose, the effects of daily handling and maternal separation (3 min per day) on both behavioral and cardiovascular measures were examined in spontaneously hypertensive (SHR) and normotensive control Wistar Kyoto (WKY) rats. Prior to weaning, elevated heart rates in pups handled during the first postnatal week were most pronounced among 4-week-old prehypertensive SHR pups. Early handling affected behavior observed during open-field testing similarly in young adult rats of the SHR and WKY strains (e.g., increased locomotor activity on the first day of testing). In female rats of the WKY strain, early handling resulted in a lower baseline blood pressure; the blood pressure of SHR rats was not affected by increased stimulation in infancy. Examination of longitudinal data yielded no support for a direct association between behavioral reactivity or preweanling heart rate and high blood pressure. These findings demonstrate the influence of both early environmental conditions and genetic factors on maturation within the cardiovascular system and suggest that genetic models of pathological conditions may provide a productive means of examining environmentally shaped aspects of individual differences in physiological regulation.

Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: neurochemical effects in the spinal cord

The effects of s.c. capsaicin treatment on the thoracic spinal cord contents of immunoreactive substance P (ISP), norepinephrine (NE) and serotonin (5-HT) were investigated in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Capsaicin administered s.c. significantly reduced the concentration of ISP in the thoracic spinal cords from rats of both the WKY and SHR strains. The s.c. administration of capsaicin significantly increased the NE contents of the thoracic spinal cords in rats of both the WKY and SHR strains, and both vehicle- and capsaicin-treated SHR animals exhibited significantly greater thoracic spinal cord NE concentrations than did rats from the corresponding WKY treatment groups. In contrast, s.c. capsaicin treatment significantly increased the concentration of 5-HT only in the thoracic spinal cords of SHR subjects. These results strongly suggest that the neurochemical effects of s.c. capsaicin administration on the spinal cord were not specific to ISP-containing neurons since significant changes in the concentrations of NE and 5-HT were also produced by capsaicin treatment. These capsaicin induced changes in the concentrations of putative neurotransmitter substances in the spinal cord are related to previously reported alterations in nociception and cardiovascular regulation produced by s.c. capsaicin administration. Physiological and pharmacological mechanisms possibly relating the neurochemical changes produced by capsaicin to the behavioral and cardiovascular effects of the drug previously reported are advanced and discussed.

Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: Effects of substance P contents of peripheral and central nervous system tissues

The effects of s.c. capsaicin treatment on the contents of immunoreactive substance P (ISP) in several peripheral and central nervous system tissues were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Significant differences between vehicle-treated subjects of the WKY and SHR strains were observed in the ISP contents of both superior cervical and celiac sympathetic ganglia. Capsaicin pretreatment significantly reduced the ISP contents of both sympathetic ganglia in both strains. Capsaicin pretreatment significantly elevated the ISP contents of adrenal medullae only in rats of the SHR strain. The effects of s.c. capsaicin administration on the ISP contents of several selected isolated brain nuclei were also examined. No statistically significant strain or treatment differences in the ISP contents of the nucleus tractus solitarii nucleus ceruleus and periaqueductal central gray were observed. The ISP contents of the nucleus raphe magnus, periventricular preoptic area, and nucleus amygdaloideus medialis were significantly greater in vehicle-treated SHR rats than in vehicle-treated WKY animals. Capsaicin pretreatment significantly increased the ISP contents of both the periventricular preoptic area and nucleus amygdaloideus medialis in rats of the WKY strain. Capsaicin pretreatment also significantly decreased the ISP content of the nucleus amygdaloideus medialis in SHR rats. These results indicate that the effects of capsaicin treatment of the ISP contents of nervous systems tissues vary with both the tissues examined and the strain of rat. In addition, the previously reported long-lasting hypotensive effect produced by capsaicin in both the WKY and SHR strains may be related to the significant depletion of the ISP contents in peripheral sympathetic ganglia in both strains.

Altered inotropic responsiveness to isoproterenol of hearts from spontaneously hypertensive rats during development.

The characteristics of the inotropic responses to isoproterenol (Iso) were investigated in isolated hearts from embryonic normotensive (NT) and spontaneously hypertensive (SH) Wistar-Kyoto rats at 14, 16, 18 and 20 days of gestation and from rats 3 and 10 weeks after birth and in ventricular strips prepared from hearts of newborn and 1-week-old rats. With rates of all preparations maintained constant by electrical stimulation, concentration and age dependent increases in contractility in response to Iso, capable of being blocked by propranolol, were observed. In embryonic hearts, irrespective of Iso concentration or embryonic age, similar effects were observed in hearts from NT and SH animals. However, in all postnatal preparations, the effects of Iso on the SH strain were quantitatively different from those on hearts of NT rats of the same age. As early as 12 hr after birth and through 10 weeks of age, most concentrations of Iso induced inotropic effects that were significantly greater in hearts of the SH than the NT strain and the slopes of the linear portions of the concentration-response curves were significantly steeper. These findings indicate that functional beta adrenergic inotropic receptors are present in the embryonic hearts of both strains and undergo changes during development that are strain dependent.

Alcohol-induced redox changes in the liver of the spontaneously hypertensive rat: Effect of chronic ethanol treatment

Acute ethanol administration (1.0 g/kg, i.p.) to naive, chow-fed male spontaneously hypertensive (SH) rats (4–13 weeks of age) had no effect on the hepatic lactate/pyruvate (L/P) ratio, whereas this ratio was elevated significantly in male Wistar rats. The β-hydroxybutyrate/acetoacetate (B/A) ratio in the liver was increased in both male SH and male Wistar rats. As in the male Wistar rats, the acute administration of ethanol led to significant elevation of the hepatic L/P and B/A ratios of females of both the SH and Wistar strains. Acute ethanol administration to chronically ethanol-fed male SH rats, in which the ethanol metabolic rate was 100 per cent higher than in controls, resulted in significantly elevated hepatic L/P and B/A ratios. Chronic ethanol administration to male SH and male Wistar rats led to marked development of metabolic tolerance in the former and to moderate tolerance in the latter. In addition, alcohol dehydrogenase (ADH) activity was elevated significantly in the ethanol-fed male SH rats, but not in the ethanol-fed male Wistar rats. The present work extends our recent observations that ADH primarily determines ethanol metabolism in the male SH rat.

Electron-microscopic studies on reaggregate cultures of vascular smooth muscle cells from normotensive and spontaneously hypertensive rats.

Vascular smooth muscle cells were taken from the aortae of the WKY (normotensive) and SHR (spontaneously hypertensive) strains of rat by enzymatic dispersion and put into reaggregate culture. Initially the cells became individual spheroids having average diameters of 10 micrometers and surfaces that were either rough or smooth. The cells were far more complex than they appeared on their surfaces; after one day in culture, there was considerable internal variation in these cells. All the cells, whether WKY or SHR, lost the bulk of their cytoplasmic contents (including myofilaments, many mitochondria, and vesicular structures) in the early stages of culture and eventually became flattened. After 14 days in culture, these modified cells collected to form reaggregates that were commonly roughly spherical and several hundred micrometers in diameter. These reaggregates consisted of peripheral regions made up of several layers of flattened cells overlying cores formed by glia-like networks of cells similar in cytological appearance to the cells at the periphery. The meshes formed in this way contained cellular debris derived from dead cells or extrusion of cellular contents. It appears that SHR cells are quicker to form reaggregates than are WKY cells. Yet the SHR cells retained a rounded conformation after five days, whereas the WKY cells were more flattened and formed a more discrete aggregate at this stage of culture. However, by the fourteenth day of culture, differences between the two cell strains were not so pronounced, as far as could be judged by observations made with scanning and transmission electron microscopy. Both WKY and SHR cells at 14 days appeared highly secretory, possessing large Golgi systems as well as numerous ER cisternae and mitochondria. SHR cells produced greater amounts of connective tissue at all stages of culture than did WKY cells, indicating that a similar difference may contribute to the hypertension which develops naturally in situ in SHR animals.

Urinary kallikrein excretion in a spontaneously hypertensive strain of rats.

Concentration and 24-hr excretion of urinary kallikrein in spontaneous hypertensive Wistar strain rats of both sexes obtained by selected inbreeding (25th generation) are significantly decreased as compared with the excretion in normotensive inbred rats (24th generation) descending from common ancestors. Apparently in these hypertensive rats there is an abnormal capacity of the kidneys to produce or release kallikrein, but more studies will be necessary to correlate this findings with blood pressure increase.