Adrenal mitochondrial and serum corticosteroid studies in rats resistant to adrenal-regeneration hypertension (ARH).

Female rats of the Wistar-Furth (W/Fu) strain appear to be resistant to the development of adrenal regeneration hypertension. At a time period, after adrenal enucleation, when Holtzman female rats had elevated serum 11-deoxycorticosterone levels and were hypertensive, none of the W/Fu rats became hypertensive. In vitro adrenal studies after quiescent kills of W/Fu rats indicated that cholesterol side chain cleavage activity was greater in mitochondria from regenerating adrenals than from controls. Both serum deoxycorticosterone and corticosterone levels were significantly greater in the adrenal-enucleated group. These studies were repeated in animals which were given a standard ether anesthetic stress. Ether stress increased cholesterol side chain cleavage activity comparably in control and adrenal-enucleated rats and also increased their serum deoxycorticosterone and corticosterone levels. Adrenal-enucleated Wistar-Furth rats had higher serum deoxycorticosterone levels than controls, whereas controls had higher serum corticosterone levels than the adrenal-enucleated group after the ether stress. These results indicate that although the adrenal-enucleated W/Fu rats have increased serum deoxycorticosterone levels, none of these rats develop frank hypertension. This suggests a resistance to deoxycorticosterone-induced hypertension in this strain of rat.

Methacholine-induced airway reactivity of inbred rats.

Dose-response curves to inhaled aerosolized methacholine chloride (MCh) were obtained in anesthetized spontaneously breathing rats. Thirty rats (10/strain), randomly selected from highly inbred ACI, Lewis (L), and Brown Norway (BN) strains and 40 rats (20/strain) from similarly inbred Wistar-Furth (WF) and Buffalo (Buf) strains were studied. Airway responses were quantitated from changes in pulmonary resistance (RL) and airway reactivity was calculated as the dose of MCh required to increase RL to 150% (ED150RL) and 200% (ED200RL) of base line. There were no statistically significant differences in ED150RL and ED200RL among the five rat strains. Large interindividual variability was present as evidenced by 128-fold differences in ED150RL and ED200RL between the least and most sensitive animal of the same strain. In contrast, seven animals studied repeatedly on different days had values of ED150RL that differed by an average of only 2.9-fold (range 1.6-5.3). Thirteen rats that were studied on two occasions separated by an interval of 3 mo showed no systematic changes in airway reactivity. We conclude that airway reactivity to inhaled methacholine in anesthetized nose-breathing rats is not strain related, and despite animals of a given strain being genetically identical, the variability in airway reactivity within strains suggests that environmental rather than genetic factors are the major determinants of that reactivity.

Effect of growth hormone-secreting tumors on body composition and feed intake in young female Wistar-Furth rats.

Growth hormone (GH) was elevated in young growing, intact female Wistar-Furth rats bearing growth hormone (GH1) or growth hormone and prolactin (GH3) secreting tumors. Animals were injected with GH1 or GH3 cells at 1 wk of age. Total feed intake was measured for the 8-wk period from weaning until killed at 11 wk of age. Animals were fed a commercial chow diet throughout the trial. Body composition and composition of the liver and tibialis anterior muscle were determined. Tumor-bearing rats were about 65% heavier than control rats at 11 wk of age: most of the difference in body weight gain was obtained during the last 4 wk of the trial. Total feed intake during the 8 wk after weaning was increased in both GH1 and GH3 tumor-bearing rats when compared with controls. Overall feed efficiency (grams feed consumed/gram body weight gain) was improved in tumor-bearing animals when compared with controls. The GH1 tumor-bearing rats were slightly hyperphagic during wk 8, 9 and 10 (grams feed consumed/gram body weight) when compared with controls. The total amount of body dry matter, protein and ash was increased in tumor-bearing rats when compared with controls. There was no effect on total body fat. Tumor-bearing rats had increased liver weight and increased fat, protein, RNA, DNA and dry matter content when compared with controls. Tumor induction increased the weight, total RNA and total fat content of the tibialis anterior muscle when compared with controls. There was no effect on muscle protein content.(ABSTRACT TRUNCATED AT 250 WORDS)

[4-way bred rats as experimental animals].

The present study is an attempt to utilize hybrids among several inbred strains of rats as useful animals for the studies of effectiveness and toxicology on drugs., Four-way crosses were made among the LEW, WM, F344 and DRY strains of rats, and their characteristics were examined. From the breeding data of diallel crosses among these four strains and reciprocal crosses among their F1 hybrids, the mating type indicating the highest reproductivity was (LEW X WM) F1 X (F344 X DRY) F1. These four-way crosses were designated as LWFD. The reproductivity of this mating type was exceedingly higher than those of four strains. In order to examine the susceptibility to thiamine hydrochloride, the acute toxicity test was practiced in inbred strains, F1 hybrids and four-way crosses. As a result, in spite of highly heterogeneous population, the LWFD did not show a peculiar response in comparison with four strains and their F1 hybrids. Furthermore, hematological and clinico-biochemical values of the LWFD did not show a large variability as presumed. From these results, it is suggested that hybrids such as four-way crosses among inbred strains can be used as useful animals for the studies of effectiveness and toxicology on drugs.

Resistance of W/Fu rats to adrenal regeneration hypertension.

The procedure for producing adrenal regeneration hypertension did not cause an increase in the systolic blood pressure of W/Fu animals. The regenerating adrenal gland in W/Fu animals was not restored to normal; reduced numbers of mitochondrial cristae were seen and the mitochondria were smaller in size; regeneration was complete in Sprague-Dawley rats of the Holtzman strain and there was a severe form of hypertensive, cardiovascular disease.

Protection against puromycin aminonucleoside-induced chronic renal disease in the Wistar-Furth rat.

The Wistar-Furth (WF) rat is protected against chronic renal disease (CRD) following 5/6th ablation/infarction vs. the Sprague-Dawley (SD) rat, and protection was associated with preserved renal nitric oxide (NO) production. This study examined CRD induced with repeated administration of puromycin aminonucleoside (PAN). SD PAN developed nephrotic range proteinuria (>1 g/24 h), and at 15 wk severe renal injury developed and the glomerular filtration rate (GFR) was reduced to approximately 10% of sham. Total NO production, renal NO synthase (NOS) activity, and renal neuronal (n) and medullary endothelial (e)NOS abundance were reduced in the SD PAN. WF PAN exhibited less severe initial proteinuria (>400 mg/24 h), which abated within weeks, whereas GFR was normal and injury was minimal at 15 wk. Total NO production and renal NOS activity and abundance were significantly elevated compared with SD PAN. NOS mRNA (nNOS, eNOS, and inducible NOS) was not altered in WF, whereas SD showed significant increases in NOS gene expression with PAN. In conclusion, WF showed resistance to a second model of CRD with maintained renal NOS activity compared with SD.

Nitrate production and phagocyte activation: differences among Sprague-Dawley, Wistar-Furth and Lewis rats.

We have found that activated resident peritoneal macrophages from Wistar-Furth and Sprague-Dawley rats produce significantly more superoxide (2.2 +/- 0.4 and 3.6 +/- 0.8 nmol of cytochrome c reduced/10(6) cells/10 min respectively) than those from Lewis rats (1.0 +/- 0.3 nmol of cytochrome c reduced/10(6) cells/10 min). Similar results are found in macrophages elicited with intraperitoneal thioglycolate. Furthermore, nitrate excreted in the urine increased greatly when either Wistar-Furth or Sprague-Dawley rats are injected i.p. with iota carrageenan (0.25 g), a response that did not occur with Lewis rats. This strain difference in the manifestations of the inflammatory response correlates with previous observations that Wistar-Furth and Sprague-Dawley rats, but not Lewis rats, develop suture-line colonic tumors when the ureters and bladder base are implanted into the colon.

Interaction between hypersomatotropism and age in the Wistar-Furth rat.

The purpose of this study was to examine body growth parameters and serum somatomedin levels in progressively older rats exposed to high levels of circulating growth hormone (GH). The effects of growth hormone secreting tumors arising from GH3 cell injection were evaluated in 3, 5, 9, 18 and 24 month old female Wistar-Furth rats. In all tumor-bearing rat age groups, body weights were in excess of 70% of age-matched controls. Contributing to these body weight gains were significant increases in heart, liver, kidney and hind limb muscle weights. Fat pads from the tumored groups were similar to controls in the young (3, 5, 9 month) rats but were significantly smaller in the older groups at 18 and 24 months. Elevated GH predictably increased somatomedin levels in young rats while in the 18 and 24 month old groups, smaller increases were noted. These results show that old rats respond to GH in a mechanism involving somatomedin and that significant increases in somatic growth can be obtained, even at advanced age.