摘要:

In the rat model of chronic myocardial infarction the border or "transition zone," extending 225–525 μm from the margin of the scar, is supplied by significantly fewer capillaries and characterized by an altered capillary-fiber geometry when compared with healthy rat myocardium. Four weeks of daily voluntary running can, under certain conditions, promote capillary growth and a shift in capillary-fiber geometry, such that a normal capillary supply is restored to the transition zone. However, the importance of exercise frequency, intensity, and duration for capillary growth in the transition zone has not been determined. One week after surgical occlusion of the left coronary artery, rats were divided into four groups following different protocols of voluntary exercise (running): A (2 h/day, 6 days/week for 4 weeks), B (2 h/day, 3 days/week for 4 weeks), C (2 h/day, 6 days/week for 2 weeks, followed by 2 weeks sedentary), and D (2 h/day, 6 days/week for 2 weeks). Significant improvements in capillary supply to the transition zone were associated with voluntary exercise, three separate factors being of importance, (i) An intermediate total distance run; rats that ran 5–10 km in the month restored a normal number of capillaries and a normal capillary-fiber geometry in the transition zone, whereas rats that ran either <5 or >10 km showed no significant improvements. (ii) A balance between exercise frequency and mean distance ran per 2-h exercise period; rats in group B (3 days/week) had to run twice the daily distance of those in group A (6 days/week) to obtain the same improvement in capillary supply. (iii) Regular reinforcement of the exercise periods throughout the experiment; animals in groups B and D demonstrated significant increases in capillary supply in the transition zone, while those in group C did not. Although exercise stimulates capillary growth and a shift in capillary-fiber geometry in the transition zone, the mechanisms underlying these improvements are, as yet, unknown.

ISSN:0008-4212    

DOI:10.1139/y85-049

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Perinatal thyroid dysfunction in the rat leads to permanent alterations in pituitary TSH secretion in the adult animal. Thus, neonatal hyperthyroidism (NH) and perinatal hypothyroidism (PH) both result in apparent increased pituitary sensitivity to the feedback effects of thyroid hormones in the adult rat. To determine if increased intrapituitary generation of triiodothyronine (T3) might account for these observations, we measured thyroxine (T4) 5′-deiodinase activity in pituitary homogenates of adult NH and PH rats. NH was induced by injecting neonatal rats with 12 daily sc injections of T4(0.4 μg/g body weight (BW)). Control rats received vehicle alone. PH was induced by administering 0.05% 6-n-propylthiouracil in the drinking water to pregnant dams from the 16th day of gestation through the 12th day postpartum. Thereafter, a normal water supply was substituted. NH and PH rats were allowed to mature and were sacrificed at 105 days of age. Serum T4, T3, and TSH concentrations were measured by radioimmunoassay. Pituitary T45′-deiodinase activity was assessed by the measurement of T3formation by pituitary homogenates incubated in the presence of 0.65 μM T4and 100 mMdithiothreitol at 37 °C for 90 min. Body weights of adult NH and PH rats were slightly but not significantly decreased compared with control rats. Relative pituitary gland weight (milligrams per 100 g BW) was significantly decreased in adult PH rats (P < 0.005) but not in adult NH rats. In adult NH rats, serum T4and T3concentrations were significantly decreased (P < 0.01) compared with control rats. Serum TSH concentrations were similar. No significant differences in serum T4, T3, and TSH concentrations were noted between adult PH and control rats. Pituitary T45′-deiodinase activity was significantly increased in both adult NH and PH rats compared with controls (NH > PH > control;P < 0.005, andP < 0.05, respectively). These data indicate that pituitary T45′-deiodinase activity is significantly increased in adult NH and PH rats. Increased pituitary T45′-monodeiodination may explain, in part, the apparent increased thyrotroph sensitivity to feedback effects of thyroid hormone in these animals.

ISSN:0008-4212    

DOI:10.1139/y85-050

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The effects of piretanide upon mechanical activity and pharmacological reactivity of vascular and myocardial tissues from normotensive rats were investigated. Magnitude of phasic contractions of isolated rat portal vein was diminished by the drug in a dose-related manner; contractile depression induced by piretanide (10−4 M) was less in the presence of insulin (0.1 U/mL), glucose (22 mM) or pyruvate (5 mM). Responses to KCl (90 mM), or norepinephrine (2.5 × 10−5 M) were also reduced. Contractile activity of atria and ventricle strips was diminished only when piretanide reached 10−4 M. Results support direct actions of piretanide upon cardiac and vascular tissues. Possible mechanisms of action are discussed.

ISSN:0008-4212    

DOI:10.1139/y85-051

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Experiments were performed on isolated detrusor smooth muscle from New Zealand White rabbits. Oxytocin was shown to exhibit high intrinsic contractile activity on isolated strips of detrusor muscle, where the maximum contractile amplitude was 12% greater than control responses to 1 μMcarbachol. Repeated applications of 1 μMoxytocin were associated with tachyphylaxis representing a 49% decrease in the amplitude which became reproducible after several applications without further decay of contractile strength. Dose–response experiments indicated that threshold contractions to oxytocin occur at 3 μMand were maximum at 10 μMwith mean effective concentration of 125 μM. The contractile responses to 1 μMoxytocin were not antagonized by phentolamine, atropine, methysergide, saralasin, or naloxone, but were partially inhibited by 1 μMof indomethacin. Ligand binding studies on partially purified membrane preparations from detrusor smooth muscle were performed over a range of 78 pMto 10 nMwith125I-labelled oxytocin. Scatchard analysis of specific bound receptors indicated aKDof 2.5 nMandBmaxof 187 fmol/mg protein and a second compartment that was unsaturable at the concentrations of ligand employed. Nonspecific binding ranged from 36 to 77% of the total binding.

ISSN:0008-4212    

DOI:10.1139/y85-052

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Myelinated axons ofXenopus laeviswere rapidly frozen in liquid nitrogen and thawed in a potassium glutamate based medium. Organelles within isolated, thawed axons were visualized by light microscopy. After thawing, organelles were stationary for about 5 min. Following this quiescent period, organelles exhibited a low frequency oscillation in the longitudinal direction of the axon; some of the organelles then began to move in either the anterograde or retrograde directions. Electron microscopic examination of axonal cross sections showed that few microtubules were present immediately after thawing, but the numbers of microtubules recovered to approximately normal levels with a time course closely resembling that of the recovery of organelle transport. The effects of colchicine and taxol on the recovery of organelle transport and the microtubule content of axons was consistent with the hypothesis that the recovery in microtubule numbers was related to the recovery of organelle transport. Vanadate ions inhibited the recovery of organelle transport at concentrations known to inhibit dynein ATPase.

ISSN:0008-4212    

DOI:10.1139/y85-053

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

Ketamine (1.1 × 10−5to 3.7 × 10−4 M) potentiated catecholamine responses of rat anococcygeus muscle and rabbit aortain vitro. In the anococcygeus, potentiation was abolished by cocaine (2.9 × 10−5 M) pretreatment or by chemical sympathectomy using 6-hydroxydopamine (6-OHDA), but was unaffected by pretreatment with the extraneuronal uptake inhibitor cortisol (8.3 × 10−5 M), or the catechol-O-methyltransferase inhibitor tropolone (2.4 × 10−4 M). The action of ketamine mimicked the potentiating effect of cocaine on tyramine responses. In contrast, the potentiation by ketamine in rabbit aorta was unaffected by cocaine or 6-OHDA but was abolished by cortisol or tropolone; and ketamine potentiated tyramine responses, whereas cocaine inhibited them. Thus the mechanism of action by which ketamine produces potentiation of catecholamines in these two tissues is completely different. These results suggest that ketamine has the unusual ability to block neuronal and extraneuronal uptake and that the predominating mechanism will depend on the type of tissue examined and the morphology of its adrenergic innervation.

ISSN:0008-4212    

DOI:10.1139/y85-054

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

A recently added goal in the control of primary hypertension is the reversal of left ventricular hypertrophy which may occur early in the disease and which can have serious consequences. We have attempted to define the hemodynamic parameters which distinguish most sensitively between the long-term effects of two antihypertensive drugs, alpha-methyldopa and propranolol, with a view to determining the optimal conditions under which each of the drugs may be used therapeutically. Twenty matched hypertensive patients, all with established left ventricular hypertrophy, were divided at random into two groups who received either alpha-methyldopa or propranolol as monotherapy. Dosage was titrated until blood pressures were normalized (diastolic blood pressure (DBP) ≤ 95 mmHg) (1 mmHg = 133.322 Pa); then therapy was maintained for 48–52 weeks. Supine and erect blood pressures, heart rates, and eight echocardiographic indices were recorded before commencement of therapy and at the 48- to 52-week period. Stepwise discriminant analysis identified erect DBP, erect heart rate, and posterior wall thickness of the left ventricle as being the parameters which distinguished most clearly the therapeutic effects of the chosen drugs. Using these three parameters, all 20 patients were correctly classified into their respective drug groups. We propose that these results may form the basis of a more rational choice of antihypertensive therapy with alpha-methyldopa or propranolol for hypertensive patients based on the initial determination of these three parameters.

ISSN:0008-4212    

DOI:10.1139/y85-055

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The subcellular localization of oxytocin within the corpus luteum of sheep was investigated using differential and density gradient centrifugation. Oxytocin was associated with a particulate fraction which sedimented to a density of 1.054 – 1.061 g/mL. The exclusion of [3H]oxytocin from this particulate fraction is indicative that particulate oxytocin represents endogenous compartmentalization. Particulate oxytocin, incubated in buffered medium at 37 °C, was stable for up to 1 h and the release of oxytocin was not affected by the pH of the incubation medium, over the range 5.5 – 8.5. Oxytocin release, however, was stimulated by incubating particle-bound oxytocin in buffered medium of low osmolality (<200 mosmol). These data are similar to the physicochemical properties reported for peptide-containing neurohypophysial secretory granules. Ultrastructural analysis of oxytocin-containing fractions revealed the presence of electron-dense granules (diameter, 200–250 nm). These data are suggestive that oxytocin, in the corpus luteum of sheep, is contained within a population of secretory granules which occur in high numbers during the midluteal phase of the oestrous cycle.

ISSN:0008-4212    

DOI:10.1139/y85-056

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

The disposition of valproic acid (VPA) in rabbits was studied after chronic treatment withEscherichia coliendotoxin. Endotoxin (1–2 μg/kg) was administered daily to 10 male New Zealand white rabbits for 5 days. On day 5, 50 mg/kg of VPA was given iv during the time of the peak febrile response. Blood samples were drawn at appropriate time intervals and analyzed for free and total VPA levels as well as plasma proteins and free fatty acids. The data were compared with similar control experiments performed 2 weeks before and after endotoxin treatment. Pharmacokinetic analysis indicated that the changes in free VPA clearance after endotoxin were related to the change in the febrile response during chronic treatment (r = 0.77;p < 0.05); that is, animals which developed tolerance to the febrile response showed elevated drug clearance, whereas nontolerant animals showed decreased clearance of VPA.

ISSN:0008-4212    

DOI:10.1139/y85-057

出版商:NRC Research Press    

年代:1985

数据来源: NRC

摘要:

In cultures of rat granulosa cells, luteinizing hormone-releasing hormone (LHRH) increases32P incorporation into both phosphatidylinositol (PI) and phosphatidic acid (PA). After 20 min, the level of radioactivity was three- to four-fold (p < 0.01) above control in the PI and PA fractions, respectively. The stimulatory effect of LHRH on32P incorporation was limited to PI and PA. Similar to the effects of LHRH, a rapid and marked increase of32P incorporation into both PI and PA is observed upon addition of prostaglandin F2α(PGF2α) (10−5 M) to rat granulosa cells. Incorporation of radioactivity into PA was already increased (p < 0.05) by 2 min following PGF2αaddition, while the increase in32P-labeled PI became significant (p < 0.01) by 5 min. In contrast to PGF2α, the labeling of PI and PA following the addition of PGE2(10−5 M) was not significantly different from control levels during the entire 10 min of incubation. The sensitivity of the increased PA–PI labeling induced by LHRH and PGF2αis compared in another experiment. After 20 min incubation 10−6 MLHRH increased PI and PA labeling by six-and four-fold, respectively. Although the effect of PGF2αis less than that of LHRH, 10−5 MPGF2αsignificantly (p < 0.01) increased PI and PA labeling by three- and two-fold, respectively. By contrast, 10−6 MPGE2failed to affect32P incorporation into the various phospholipid fractions, but a small enhancement (p < 0.05) of PI and PA labeling was observed only at 10−5 MPGE2. These data further support the hypothesis that LHRH and PGF2αshare a common mechanism in ovarian cells involving phospholipid metabolism.

ISSN:0008-4212    

DOI:10.1139/y85-058

出版商:NRC Research Press    

年代:1985

数据来源: NRC