Adult Male Guinea Pigs Research Articles

Effect of Linoleic Acid on Digitalis Cardiotoxicity

Adult male guinea pigs were anesthetized, catheterized and i.v. infused with either saline and then ouabain or with linoleic acid salt and then ouabain. The linoleic acid pretreatment produced a significant delay until the onset of digitalis induced cardiac arrhythmias.

Regulation of the pituitary-adrenal axis and corticosteroid-binding globulin-cortisol interaction in the guinea pig.

Adult male guinea pigs were used to examine pituitary-adrenal function and corticosteroid-binding globulin (CBG)-cortisol interaction. A biphasic pattern in the circadian rhythm of plasma cortisol was observed, with nadirs occurring at 0800 and 2400 h and peaks and 1600 and 0400 h. An excellent correlation was noted between total and free plasma cortisol levels. In contrast, no correlation was noted between CBG binding capacity and either the total or free plasma cortisol level. The free plasma cortisol concentration ranged from 0.6-5.8 micrograms/dl, representing 6.1-14.5% of the total cortisol concentration. The CBG binding capacity ranged from 12.2-161.7 micrograms/dl, and the binding affinity was 1.3-2.2 x 10(7) M-1 at 22 C, which is 20-fold lower than that of human CBG. These results suggest that CBG in the guinea pig has a relatively minor effect on the plasma distribution of cortisol, and that free plasma cortisol is dependent on cortisol binding to nonspecific plasma proteins as well as on the total plasma cortisol concentration. It was found that the guinea pig was relatively resistant to dexamethasone suppression, requiring at least 1 mg/kg BW to obtain essentially complete suppression of the pituitary-adrenal axis. In addition, it was found that administering dexamethasone 6 h before the time that the animals were killed led to suppression, whereas giving the steroid 12 h before killing the animals was totally ineffective. Stress induced by both ether vapor and histamine injection significantly increased plasma cortisol levels. When the guinea pigs were treated with a 1 mg/kg BW dose of dexamethasone 6 h before the stimulus, however, a marked suppression of the plasma cortisol increment secondary to application of the stressful stimulus occurred.

Effect of ovarian hormone pretreatment on gallbladder motility [formula omitted

Adult male guinea pigs were pretreated with estrogen, progesterone, or estrogen plus progesterone and the in vitro contractile response of the gallbladder to cholinergic stimulation examined. The data were compared with results obtained from control animals. Progesterone pretreatment was associated with a significant decrease in the maximal contractile response of the tissues and with a significant increase in the dose of acetylcholine needed to produce a threshold response. Estrogen pretreatment significantly decreased the threshold dose requirements but had no effect on maximum tension development. In addition, estrogen pretreatment antagonized the inhibitory effect of progesterone pretreatment. The data support the hypothesis that the ovarian steroid hormones can affect gastrointestinal smooth muscle. Furthermore, the hormones appear to exert independent and opposite effects on gallbladder motility. Additional studies will be required to determine the physiological significance of these observations.

Effect of Progesterone Pretreatment on Guinea Pig Gallbladder Motility In Vitro

Experiments were designed to examine the effect of chronic pretreatment with progesterone (2 mg/kg . day for 5 days) on the in vitro contractile response of gallbladder muscle strips from adult male guinea pigs. The muscle strips were challenged with either acetylcholine or the octapeptide of cholecystokinin and dose-response relationships were determined. The data were compared with dose-response curves obtained from untreated control animals. progesterone pretreatment produced right-ward shifts in the acetylcholine and octapeptide of cholecystokinin curves that were characterized by significant decreases in the maximal contractile response. Serum progesterone concentrations in the pretreated animals were significantly increased over control levels. The data support the hypothesis that the sluggish behavior of the gallbladder during pregnancy and during the luteal phase of the menstrual cycle may be due, in part, to progesterone-related alterations in the contractile properties of gallbladder smooth muscle.

Metabolism of benzo[ a]pyrene by guinea pig adrenal and hepatic microsomes

Studies were carried out to compare the metabolism of benzo[ a]pyrene (BP) by adrenal and hepatic microsomes obtained from adult male guinea pigs. Adrenal microsomes produced fluorescent metabolites (primarily phenols) approximately three to four times more rapidly than hepatic microsomes, but the differences in the rates were considerably smaller when total BP metabolism was assessed using an isotopic assay. The apparent discrepancy between the two assays is attributable to differences in the profiles of BP metabolites produced by adrenal and liver. Separation of metabolites by high pressure liquid chromatography revealed that adrenal microsomes converted BP to primarily a phenolic metabolite with a retention time identical to that of 3-hydroxy-BP. Liver microsomes, by contrast, produced approximately equal amounts of compounds co-chromatographing with 3-hydroxy-BP and BP-4,5-dihydrodiol. Small amounts of other metabolites were also produced by adrenal and hepatic microsomes. Liver microsomes catalyzed the conversion of BP to metabolites that became covalently bound to exogenous DNA. The amount of binding was dependent upon the duration of incubation and concentration of microsomal protein. Adrenal microsomes, by contrast, did not promote BP binding to DNA. Inhibition of microsomal epoxide hydratase activity with trichloropropene oxide (TCPO) blocked the formation of dihydrodiol metabolites of BP by adrenal and liver microsomes. In the presence of TCPO, liver microsomes produced large amounts of a BP metabolite co-chromatographing with BP-4,5-oxide. TCPO also increased the rate of production of DNA-binding roetabolites by liver microsomes but had no effect on the formation of DNA-binding metabolites by adrenal microsomes. The results demonstrate major differences in the pathways of BP metabolism by guinea pig adrenal and hepatic microsomes. Although adrenal microsomes metabolize BP more rapidly than hepatic microsomes, far greater amounts of reactive metabolites are produced by the liver. Thus, adrenal metabolism of BP may be of little toxicological significance.

Measurement of the rate of secretion, peripheral metabolism and interconversion of cortisol and cortisone in adult conscious male guinea-pigs

Metabolism of the cortisol (F) and the cortisone (E) was studied by continuous infusion of [ 14c]-F and [ 3H]-E in adult conscious male guinea-pigs. Parameters, calculated from the specific activities of F and E, are expressed in μmoles/24 h : production rate of F (PR F) =8 ± 1 and E (PR E) = 4.9 ± 0.7; secretion rate of F (Q F) = 7.1 ± 0.9 and E (Q E) = 0.9 ± 0.4; rate of irreversible metabolism of F (rF) = 6.2 ± 0.9 and E (rE) = 1.8 ± 0.3; percentage of transfer of F into E = 59 ± 4% and E into F = 80 ± 3%. These results demonstrate that adrenal gland in the adult male guinea-pig secretes essentially cortisol and little or no cortisone. Practically all the pool of E is derived from transformation of F into E; the major part of E production is reconverted into F.

Hormonally responsive areas of the reproductive system of the male guinea pig. III. Presence of cytoplasmic estrogen receptors.

We have previously shown that the administration of estrogens to intact adult male guinea pigs resulted in a variety of morphological changes in their accessory sex organs (the seminal vesicles, prostate, common ejaculatory chamber, coagulating gland, and epididymis). To ascertain if a biochemical basis existed for a direct action of estrogens on these tissues, we examined them for the presence of estrogen receptors. We determined that cytosol prepared from the accessory sex glands contains a macromolecular binding component for estradiol-17�. This component sediments as an 8S species on 5-20% sucrose gradients under low (0.01 M KCI) ionic strength conditions and as a 4S species under high (0.4 M KCI) ionic strength conditions. Time-course studies indicate that binding equilibrium is achieved in �\�2 h; dissociation of [3 HI estradiol from the binding protein is very slow (t#{189}>42 h). The cytoplasmic binder is highly specific for estrogens; the relative affinities of various estrogens for the protein were estradiol = 1, estrone = 0.72, diethylstilbestrol 0.30, and estriol = 0.17. Progesterone, testosterone, and 5a-dihydrotestosterone, even at a 1000-fold excess, caused less than 10% inhibition of [3 HI estradiol binding to the protein. The binder present in cytosol prepared from the accessory sex organs (excluding the epididymis) exhibited an equilibrium dissociation constant of ‘��0.3 nM, and there were “.‘30 fmoles of binding sites per mg of cytosol protein. The cytoplasmic estrogen binder exhibits the characteristics usually attributed to receptors and is clearly different from a 4S, nonspecific, rapidly dissociating binder that is present in plasma. On the basis of steroid specificity, the cytoplasmic estrogen binder is distinct from the androgen receptor that is present in male reproductive tissues.

Characterization of the hyperlipidemia in guinea pigs induced by 2,3,7,8-tetrachlorodibenzo- p-dioxin

Treatment of adult male guinea pigs with a single dose of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), 6.2 nmol (2.0 μg)/kg body wt, induces a marked hyperlipidemia characterized by a 19-fold increase in very low density lipoproteins (VLDL) and a 4-fold increase in low-density lipoproteins (LDL) compared to pair-fed control animals. VLDL from TCDD-treated animals were similar in size and electrophoretic mobility to VLDL from pair-fed control animals, but they contained less cholesteryl ester and an altered pattern of C apoproteins on sodium dodecyl sulfate-polyacrylamide gels. LDL from TCDD-treated animals were larger than LDL from pair-fed controls and contained more phospholipid and less protein than LDL from pair-fed control animals. In addition, LDL from TCDD-treated animals contained increased amounts of apoprotein C as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. No change in the concentration or properties of serum high-density lipoproteins was observed. Serum free fatty acids, triglycerides, and cholesteryl esters from TCDD-treated animals were enriched in linoleic acid (18:2), a principal fatty acid of adipose tissue. This suggests that mobilization of adipose tissue fatty acids in TCDD-treated animals may lead to increased hepatic lipoprotein production. However, weight-paired control animals did not become hyperlipidemic. Thus, in addition to mobilizing adipose tissue fatty acids, TCDD may alter the relative rates of anabolic and/or catabolic processes controlling serum VLDL and LDL concentrations in the guinea pig.

Cross-species rearing influences urine preferences in wild guinea pigs

Urine preferences of adult wild male guinea pigs reared with domestic female guinea pigs were studied. Subjects were removed from the mothers at birth and each was reared with a domestic female for either the first 3 or the first 16 weeks of life; each control group male was reared with a wild female for the first 3 weeks of life. Following rearing experience, males were reared in social isolation. A series of urine preference tests was conducted beginning when the subjects were 17 weeks of age. Whereas males in the control group preferred urine of wild animals to urine of domestic animals, individuals reared with a domestic female generally preferred domestic female urine to wild female urine and were equally attracted to male urine of the two species. It is concluded that postnatal prepubertal experience influences urine odor preferences in wild male guinea pigs.

Effects of acute neurotrophic stress on peripheral metabolism of cortisol in conscious male guinea-pigs.

Cortisol metabolism was studied in conscious adult male guinea-pigs subjected to a neurotrophic stress (immobilization and stimulation by light for 3 h). The disappearance curves of tracer quantities of [3H]cortisol were represented by a two-pool model. In stressed animals, there was marked increase in the mean plasma level of cortisol (184% of control value; P less than 0.001) and in the metabolic clearance rate (MCR; 17% of control value; 0.001 less than P less than 0.001). This rise in the MRC of plasma cortisol resulted from an increase in the mean total apparent volume of distribution (49%, P less than 0.001). The lack of significant differences in the slopes of the second exponential phase of the disappearance curves indicated that the stress did not significantly increase the half-lie of cortisol. The mean binding capacity of transcortin for cortisol (ST) was significantly higher in the animals which had been subjected to the neurotrophic stress than in the control guinea-pigs (0.02 less than P less than 0.05). However, ST values remained very low and accounted for the very high levels of free cortisol found after the stress. The results suggest that the raised concentrations of unbound cortisol found in the plasma of conscious adult male guinea-pigs in response to neurotrophic stress reflect a hypersecretion of corticosteroid.

Can androgens alone fully restore seminal vesicle epithelium?

AbstractThe purpose of this work was to determine if injected testosterone alone could restore the involuted seminal vesicle epithelium of hypophysectomized guinea pigs. Adult male guinea pigs were castrated, hypophysectomized, or hypophysectomized and castrated. Seminal vesicle epithelium was then isolated, weighed, analyzed for cytoplasmic protein content, and studied for its ability to synthesize four soluble, cell-specific, secretory proteins in vitro using immunoprecipitation techniques. Hypophysectomy, like castration, caused profound involution of this androgen-dependent tissue including loss of its protein-synthesizing capability. Testosterone replacement therapy restored wet weight, general cytoplasmic protein content, and in vitro protein synthesis to values found in castrated guinea pigs given testosterone. Thus, with regard to the parameters studied, the tissue responded to testosterone alone without apparent need for a pituitary hormone. Under the experimental conditions the administration of...

2,3,7,8-Tetrachlorodibenzofuran tissue distribution and excretion in guinea pigs

The tissue distribution and excretion of [ 14C]2,3,7,8-tetrachlorodibenzofuran (TCDF) in adult male guinea pigs was studied up to 9 days following an iv or po administration (6.0 μg/kg, 0.02 μmol/kg). Greater than 90% of the dose was absorbed after po administration. Tissue concentrations and excreta were examined for [ 14C]TCDF-derived material for periods ranging from 1 hr to 9 days after administration. Liver, muscle, skin, and adipose tissue were found to be the most important tissues for the distribution of this compound. The highest levels of radioactivity were initially located in the liver and muscle, and then redistributed to the skin and adipose tissue. At 1 day the radioactivity began to be redistributed back to the liver; this second redistribution appeared to be due to the mobilization of fat stores associated with the overt toxicity of TCDF. At all time points, the specific activity of TCDF-derived radioactivity (percentage dose/g tissue) was highest in liver, fat, and adrenals, respectively. The initial phase for the elimination of radioactivity from the liver and muscle had a half-life of 3.9 and 15.7 hr, respectively. Excretion in the urine and feces each accounted for only 6.6 and 6.5% of the dose, respectively, during the 9 days following administration. Greater than 90% of the extracted radioactivity in feces and tissues examined cochromatographed with parent TCDF. However, the radioactivity in the urine did not chromatograph with TCDF and appeared to be a metabolite(s) more polar than TCDF. Studies of the accumulation and distribution of TCDF-derived material after six or more weekly doses of 1 μg/kg TCDF each demonstrated that TCDF is accumulated in liver, adipose tissue, and skin, and that when a body burden of approximately 5.6 to 6.6 μg/kg was attained, the toxicity of this compound was irreversible and resulted in progressive weight loss and death.

Effects of immunization with Freund's complete adjuvant and isologous spermatozoa on the seminiferous epithelium and blood-testis barrier in guinea pigs.

In order to gain insight into the earliest pathological changes underlying the development of autoimmune aspermatogenic orchitis (AIAO) the blood-testis barrier was studied by light and electron microscopy, freeze-etching, and cytochemical techniques early (from 1 to 8 days after adjuvant treatment of isoimmunization). At later times (16 to 21 days) the study was carried out by light microscopy only. Adult male guinea pigs were used either as controls or immunized with Freund's complete adjuvant alone or together with pertussis vaccine. An additional group comprised animals immunized with a suspension of isologous spermatozoa emulsified in Freund's complete adjuvant and with pertussis vaccine. Ultrastructural studies of the testes of experimental animals showed, at earlier periods, apparently normal Sertoli junctions. However, in the adluminal compartment, distended gaps were seen between the facing membranes of adjacent Sertoli cells. At later periods, a massive destruction of the germinal cells were observed. In freeze-fracture replicas, the Sertoli junctions of testes belonging to all the experimental groups were characterized by an irregular network of occasionally interrupted strands of particles associated with the P face (PF). Large concavities determined distensions between interconnecting ridges. The gap junctions were increased in number and in surface. Tracer studies using horseradish peroxidase showed that the marker permeated the myoid cells of a greater proportion of tubules than in control animals. Within the seminiferous epithelium there was only a limited passage of the marker towards the lumina of the tubules. Yet the tracer was always excluded from the adluminal compartment by the Sertoli tight junctions. Our observations suggest the possibility that the FCA causes a loosening of the Sertoli junctions. This condition could enhance exchanges between two antigenically different cellular compartments and, thus, favor occurrence of an autoimmune reaction when cytotoxic factors are experimentally induced, as in iso- or autoimmunization.

Induction of cell-mediated immunity to HBsAg polypeptides.

Adult male guinea pigs were immunized with hepatitis B virus polypeptides prepared by Triton X-100 solubilization of purified 22-nm hepatitis B surface antigen (HBsAg) particles. A virus-specific subunit containing both the 28,000 molecular weight glycoprotein and the 23,000 molecular weight protein stimulated both cell-mediated and humoral immunity. A whole-blood-cell transformation assay additionally showed that the 64,000 molecular weight component of HBsAg, previously shown to contain host-specific antigens, also stimulated a cellular response to purified intact HBsAg particles, suggesting the additional presence of virus-specific material in this fraction. Immunization of animals with the 28,000--23,000 molecular weight polypeptides subsequently prepared in micelle form enhanced the demonstration of a cell-mediated reaction after only a single dose of immunogen. The results provide further evidence as to the suitability of HBsAg polypeptides prepared by Triton X-100 solubilization for hepatitis B prophylaxis.

Increased capillary supply in skeletal muscle of guinea pigs acclimated to cold

The ATPase technique was used to visualize blood capillaries and to study fiber composition in 10-μm transverse sections of guinea pig gastrocnemius and soleus muscles. A control group of newborn, weanling, juvenile and adult male guinea pigs (GP) (BW = 89−1274 g) was studied in a 20–24 °C environment (22 °C GP) while 2–3 week old animals were exposed continuously to 5 °C for 2–18 weeks before sacrifice (5 °C GP) (BW = 239−1074 g). Both weight gain was not affected by cold exposure; however, the gastrocnemius and soleus muscles of the 5 °C GP grew at a slower rate than did the muscles of the 22 °C GP. The equations relating fiber cross sectional area (FCSA) and muscle weight (MW) were not different between the 22 °C GP and 5 °C GP for the soleus and gastrocnemius. Therefore, in both muscles at the same BW, FCSA was smaller in the 5 °C GP than in the 22 °C GP. In both of the two muscles of each group, capillary density (CD) decreased hyperbolically with increasing FCSA, while the capillary to fiber ratio (C/F) and the average number of capillaries around each fiber (CAF) increased linearly with increasing FCSA. The regression lines for CD, C/F and CAF versus FCSA for both muscles were parallel between groups, but at any FCSA, the CD, C/F and CAF were greater in the 5 °C GP than in the 22 °C GP. Percent fiber composition of the gastrocnemii of the 22 °C GP and 5 °C GP were not different; however, at the same FCSA each fiber type had a greater capillary supply in the 5 °C GP. The increased capillarity in the gastrocnemius and soleus muscles of the 5 °C GP suggests an improved capacity for oxygenation, a response which would correlate well with the increased oxygen utilization during prolonged cold exposure.

Stereological analysis of the guinea pig adrenal: effects of dexamethasone and ACTH treatment with emphasis on the inner cortex.

This paper describes the morphological responses of adult male guinea pig adrenals to dexamethasone (DEX) and adrenocorticotrophic hormone (ACTH), in both qualitative and quantitative terms. Most organelles and inclusions are affected, but their responses often vary in the different cell types examined: zona fasciculata externa and interna, and zona reticularis. Following DEX the volume of lipid droplets increases in cells of zona fasciculata externa but decreases in zona reticularis; smooth endoplasmic reticulum decreases in fasciculata externa but increases in reticularis. Following ACTH, exactly the opposite occurs. This strongly suggests differing functions for these subcellular entities in each cell type, particularly for the smooth reticulum, as well as for the cells themselves. The volume of the Golgi complex markedly decreases following DEX in all cells but increases only in zona fasciculata interna and zona reticularis following ACTH. These deeper cortical cells are known to secrete at least one sulfated steroid, dehydroepiandrosterone sulfate, and these changes in the Golgi complex strengthen the suggestion that the Golgi plays a role in sulfation of steroids. Mitochondrial volume and number decrease in all cells following DEX, supporting their role in steroidogenesis. Further decreases in their volume, accompanied by increases in their number following ACTH, may be related to a proliferation of mitochondria in response to ACTH. Changes in peroxisome volume and number, following DEX and ACTH, suggest a possible role for these organelles in steroid cell metabolism. Lysosomes decrease in volume in all cells following ACTH. This does not support the recently suggested concept that they play a role in steroid secretion.

Cerebral and systemic amino acid metabolism in experimental acute amphetamine poisoning in guinea pigs

Protein catabolism, as measured by plasma amino acids is increased by amphetamine injection (15 mg/kg body wt) administered to 10 adult male guinea pigs. Changes in the cerebrospinal fluid were less marked than those in the plasma. The amphetamine seemed to inhibit the enzymes of the metabolic pathways that use amino acids.

Uptake and metabolism of 3H-estrone in neural and peripheral tissue of gonadectomized adult and neonatal guinea pigs

(1) Adult and neonatal male and female guinea pigs were gonadectomized, injected with 3H-estrone (40 μCi/animal) and killed 4 hr after injection. (2) All neural tissues studied (hypothalamus, amygdala, septal area, and cerebral cortex) retained significantly more radioactivity than plasma. (3) Almost all radioactivity was recovered as either estrone or estradiol-17β. (4) A greater percentage of the total radioactivity in the hypothalamus was recovered as estradiol-17β than in other brain tissues. (5) Males and females were similar in their uptake patterns. (6) Neonatal animals generally did not selectively retain tritiated estrogen in neural tissues, though their absolute values of radioactivity were higher than adults. (7) Peripheral tissues (uterus, seminal vesicles) were the only tissues in which a higher percentage of radioactivity was recovered as estradiol-17β than as estrone. (8) Results are discussed in terms of the hypothesis that estrone must be converted to estradiol-17β for it to facilitate lordosis behavior.

Effect of naloxone and morphine on guinea pig tonic immobility

Toxic immobility produced by placing male adult guinea pigs on their backs was dose-dependently facilitated by ip morphine-SO 4 (0, 1.2, 6, and 30 mg/kg), but not significantly affected by ip naloxone-HCl (0, 0.6, 3, and 15 mg/kg). However, 2 mg/kg naloxone (ip) significantly reduced the facilitation of tonic immobility produced by 30 mg/kg morphine. The morphine effect is consistent with a role for endogenous opioid peptides in tonic immobility. The naloxone data, however, indicate that μ-opiate receptor involvement is unlikely.

Chemical communication in Cavia: Responses of wild ( C. aperea), domestic ( C. porcellus) and F 1 males to urine

Urine preferences of wild ( Cavia aperea), domestic ( C. porcellus), and F 1 adult male guinea pigs were investigated. Males of all three types preferred female urine to male urine regardless of donor type. When given a choice between female urine of each type, males preferred conspecific urine. In choices between male urine of the three types, a conspecific preference was evident for wild and domestic but not f 1 subjects. These data indicate that a loss of distinctive male and female odours has not occurred as a result of domestication. However, the urine odours of wild and domestic types have diverged. The possible effects of previous individual experience on the preferential response is discussed.