Age In Spontaneously Hypertensive Rats Research Articles

Determination of percent area density of epithelial and stromal components in development of prostatic hyperplasia in spontaneously hypertensive rats

Objectives To determine the percent area density of epithelial and stromal components in the development of prostatic hyperplasia in spontaneously hypertensive (SH) rats. Methods The ventral lobes of prostates obtained from male SH rats and their normotensive counterparts, Wistar Kyoto (WKY) rats, were examined histopathologically at 15, 29, 40, and 54 weeks of age (5 SH and WKY rats each at each age group). The degree of prostatic hyperplasia was evaluated with a score-chart protocol, histoscore. The percent area density of epithelium and stroma of the ventral prostate were determined using a computerized image analysis system. Results Definite lesions of hyperplastic changes were demonstrated in the ventral prostate of SH rats from 15 to 54 weeks. In comparison with WKY rats, SH rats showed a significantly increased degree of prostatic hyperplasia as reflected by the histoscore values. Furthermore, the histoscore of the ventral prostate of SH rats increased with age (from 21.7 ± 0.7 at 15 weeks to 26.1 ± 0.4 at 54 weeks). The percent area density of epithelium and stroma were significantly increased in SH rats, and the ratio of stroma to epithelium ranged from 1:2.94 to 1:3.50 in SH rats but was maintained at 1:1.15 to 1:1.19 in WKY rats during the observation period. Conclusions The hyperplastic changes of the ventral prostate may develop with advancing age in SH rats. The development of prostatic hyperplasia may result from both epithelial and stromal proliferation and may be predominantly expressed as a glandular type in SH rats.

Changes of plasma L-arginine levels in spontaneously hypertensive rats under induced hypotension.

Nicardipine, a dihydropyridine type calcium channel blocker, was infused at two flow-rates into spontaneously hypertensive (SH) and control normotensive Wistar-Kyoto (WKY) rats (young, 6-week-old and adult, 23-week-old, n = 5) under pentobarbital anesthesia, to cause hypotension. Mean arterial blood pressure and the concentrations of plasma amino acids and norepinephrine (NE) were measured before infusion and at each step of the infusion. The reduction in blood pressure caused by nicardipine induced a decrease in plasma L-arginine concentration in both young and adult SH rats, this effect being larger in adult rats. There was no significant change in plasma levels of L-arginine in age-matched WKY rats. The concentration of other amino acids did not change in both rat strains. On the contrary, there was an increase in plasma NE concentration in both SH and WKY rats after infusion with nicardipine. Plasma L-arginine concentration showed a good inverse correlation with the logarithm of plasma NE concentration in SH and WKY rats and the correlation was expressed as Y = -alpha log(X) + m (Y, plasma L-arginine concentration (nmol/mL); X, plasma NE concentration (pmol/mL); alpha, a slope; and m, an intercept). alpha, 43.0 and 4.35 for 23-week-old SH and WKY rats, respectively, and 17.0 and 4.0 for 6-week-old SH and WKY rats, respectively. The present data together with previous data suggest a direct noradrenergic stimulation of the synthesis of nitric oxide (NO) from L-arginine. The findings also indicate an impairment of the L-arginine metabolism or pools in SH rats compared with WKY rats. The deficiency of L-arginine increases with the age of SH rats and could be related to the development and maintenance of hypertension due to inefficient production of NO.

Loss of basic fibroblast growth factor in the subcommissural organ of old spontaneously hypertensive rats

The immunocytochemical localization of basic fibroblast growth factor (bFGF) was studied in subcommissural organ (SCO) of aged-matched normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive (SH) rats at 10, 14 and 18 months of age using a polyclonal antibody against bFGF. The bFGF-like immunoreactivity (bFGF-ir) was observed in SCO ependymal cells of young and old normotensive rats. However, a progressive loss of bFGF-immunopositive ependymal SCO cells was observed with age in SH rats (27.24, 57.5 and 96.9% in 10, 14 and 18 months old respectively) compared with aged-matched WKY normotensive rats. Considering the potential role of the SCO in sleep regulation and sodium homeostasis, which are altered in essential hypertension, these data show a new neuroendocrine anomaly to be added to the many others previously observed in this rat strain, when they develop hypertension as they get old.

Changes in the concentration of endothelin-1 during development of hypertensive rats.

The concentration of endothelin-1 (ET-1) in the brain regions, heart, and throacic aorta of 1-, 4-, 6- and 8-week-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined using radioimmunoassay. ET-1-like immunoreactivity in the brain regions of 1-week-old WKY and SHR rats was lower compared to older (6 and 8 weeks) rats. ET-1 levels in the central nervous system gradually increased with age in both SHR and WKY rats. However, the concentration of ET-1 in 8-week-old rats was lower in the brain regions of SHR compared to WKY rats. The concentration of ET-1 in the thoracic aorta of SHR (224 +/- 43 pg/g tissue) rats was lower than that of WKY (452 +/- 11 pg/g tissue) rats at 1 week of age. However, ET-1 levels gradually increased with age in SHR rats. By 8 weeks of age, levels of ET-1 in SHR (623 +/- 33 pg/g tissue) rats were higher compared to WKY (439 +/- 62 pg/g tissue) rats. In the heart, ET-1 levels were similar in WKY and SHR rats at 4 weeks of age, but at 8 weeks of age ET-1 levels were higher in SHR rats (364 +/- 33 pg/g tissue) compared to WKY rats (260 +/- 31 pg/g tissue). It appears that at 8 weeks of age when hypertension is fully expressed in rats, ET-1 levels are lower in the central nervous system and are higher in the thoracic aorta and heart of SHR compared to WKY rats.

Myocardial Collagen Concentration and Nuclear Magnetic Resonance Relaxation Times in the Spontaneously Hypertensive Rat

In order to test the hypothesis that the increased myocardial collagen concentration in the older, spontaneously hypertensive (SH) rat is associated with altered T2 and T1, we performed in vitro studies of 70 left ventricles from 8-, 22-, and 33-week-old SH and Wistar-Kyoto (WKY) rats. We also measured the left ventricle/body weight (LV/BW) ratio (as a measure of hypertrophy), left ventricular water and fat content, and hydroxyproline concentration (as a measure of collagen). The LV/BW ration was not significantly different between 8-week-old SH rats and WKY rats but was significantly greater in SH rats than in WKY rats at 22 and 33 weeks of age. Comparing SH rats with WKY rats at 22 weeks of age, no significant difference existed in T1, T2, water content, or hydroxyproline concentration. However, at 33 weeks of age in SH rats compared with WKY rats, hydroxyproline concentration was significantly greater (4.3 +/- 0.6 mg/g, respectively; P less than .0005), water content was significantly greater (77.1% +/- 0.3% vs. 76.2% +/- 0.3%, respectively; P less than .0001), and T2 and T1 were significantly longer (T2: 52.6 +/- 2.1 msec vs. 48.6 +/- 2.2 msec, respectively; P less than .0001; T1: 656 +/- 14 msec vs. 619 +/- 12 msec, respectively; P less than .0001). In all SH rats combined, T2 and hydroxyproline concentration were significantly correlated (r = .63; P less than .0001). Thus, in SH rats, myocardial hypertrophy precedes increased collagen deposition. These data suggest that estimation of magnetic resonance relaxation times may permit noninvasive identification of increased myocardial collagen deposition independent from changes in myocardial hypertrophy.

Comparison of neuropeptide Y immunoreactivity in hypothalamic and brainstem nuclei of young and mature spontaneously hypertensive and normotensive Wistar-Kyoto rats.

The concentration of neuropeptide Y immunoreactivity (NPY-ir) was measured in 8 hypothalamic and 5 brainstem nuclei of 6- and 14-week-old spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Strain differences were observed in 3 hypothalamic nuclei and age-dependent changes occurred in 3 hypothalamic and 2 brainstem nuclei. In both the ventromedial hypothalamic nucleus and locus coeruleus the observed change in NPY-ir with age in SH rats was significantly different to the change observed in the WKY. These strain- and age-related differences in NPY-ir may be of relevance in the development of hypertension in the SH rat.

Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats.

1. The influence of thryoid function on the development of hypertension was studied in strains of spontaneously hypertensive (SH) and normotensive rats. 2. Surgical thyroidectomy decreased systolic blood pressure more markedly in SH rats than in normotensive rats. The effects of oral administration of 5 and 100 micrograms of thyroxine 24 h-1 100 g-1 were studied in the thyroidectomized animals. In the two strains the blood pressure returned to control levels only after administration of the larger dose. 3. The evolution of body weight, total plasma tri-iodothyronine (T3) and tetraiodothyronine (T4) concentrations were followed as a function of age in SH rats and normotensive rats from 5 to 21 weeks. At each age, SH rats showed significantly larger body weight and decreased T4 concentrations. Plasma T3 in SH rats was lower than in normotensive rats until 15 weeks of age, after which the difference was not significant. At 11 weeks, plasms free T3 and T4 concentrations were slightly lower in SH rats than in normotensive rats. 4. The more marked hypotensive effects of surgical thyroidectomy in SH rats cannot be related to increased thyroid function.