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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prior studies of proximal tubule reabsorption have failed to distinguish conclusively between a separate active K+ transport system and K+ movement linked to Na+ reabsorption. To attempt to dissociate movement of K+ from Na+ and Ca++, recollection micropuncture experiments were performed in proximal tubules of intact and thyroparathyroidectomized (TPTX) dogs under two different conditions known to inhibit Na+ reabsorption: saline expansion to 5% body wt, and 5 mg/kg acetazolamide. A control hydropenic group was also studied. Tubular concentrations of K+, Na+, and Ca++ were measured by electron probe analysis. During initial collections, mean+/-SEM tubular fluid/plasma (TF/P)(K+) was 1.07 +/-0.05, 1.05+/-0.05, and 1.00+/-0.03 in intact hydropenic (n = 7), saline (n = 6), and acetazolamide (n = 8) groups; fractional reabsorption (FR) of K+ in proximal tubules was 0.35, 0.39, and 0.31 respectively. After saline, (TF/P)(Inul in) fell from 1.81 to 1.34 (P < 0.01); (TF/P)(K+), (TF/P)(Na+), and tubular fluid/ultrafiltrate, (TF/UF)(Ca++) did not change, so that FR of all three ions fell proportionately. After acetazolamide, however, despite a 24% inhibition of FR of Na+ and Ca++, (TF/P)(K+) fell to 0.85+/-0.04 (P < 0.005) so that FR of K+ was unchanged at 0.34. In three corresponding groups of TPTX dogs, similar results were obtained. Acetazolamide (n = 7) inhibited FR of Na+ and Ca++ by 41%, but (TF/P)(K+) fell from 1.03+/-0.03 to 0.89+/-0.04 (P < 0.005) so that FR of K+ was unchanged (0.36-0.34).A separate uphill transport system for K+ in proximal tubules is therefore unmasked by acetazolamide, a drug which selectively inhibits Na+ (and Ca++) reabsorption. Saline, on the other hand, inhibits net reabsorption of all three ions, probably by increasing passive backflux via intercellular channels.
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PMID:Sodium-independent active potassium reabsorption in proximal tubule of the dog. 472 57

The concentration of thyroid hormone nuclear receptors varies from one tissue to another, the anterior pituitary (AP) gland possessing the highest. Since 3,5,3',1-triiodothyronine (T3) controls within a narrow range the secretion of TSH from the pituitary gland, this study was carried out to establish whether T3 modulates its own pituitary nuclear receptors and if so, whether this modulation is correlated with the thyroidal status and TSH secretion. Salt-solubilized T3 nuclear receptors were measured in the AP gland of thyroidectomized and intact adult male rats as well as in thyroidectomized rats treated with T3. In intact male rats the maximum binding capacity of pituitary T3 nuclear receptors (MBC-T3nR), determined by Scatchard analysis, was 578 +/- 45 fmoles T3/mg protein or 27 +/- 3 fmoles T3/AP (mean +/- SEM, n = 19). 2 weeks after thyroidectomy there was a marked decrease in serum T3 and T4 concentrations as well as in the MBC-T3nR (231 +/- 26 fmoles T3/mg protein or 9.3 +/- 1.2 fmoles T3/AP, n = 7) which was still observed 8 and 16 weeks after thyroidectomy. The affinity constant (Ka) of T3 for its pituitary nuclear receptors was significantly greater in thyroidectomized rats than in intact rats (3.61 +/- 0.70 vs. 1.09 +/- 0.15 X 10(10) M-1, P less than 0.001). To test whether treatment with T3 would restore a normal MBC-T3nR, 2-week thyroidectomized rats were injected with T3(0.5 micrograms/100 g b.w.) and killed 10 min, 1, 3, 15 or 24 h after T3 injection. 10 min after T3 injection MBC-T3nR was not altered but it returned to normal values 1 h after injection (441 +/- 97 fmoles T3/mg protein) and was maintained so for at least 3 h. 15 h after T3 injection MBC-T3nR was again decreased in spite of serum T3 levels that were twice as high as in normal rats. In contrast, when T3 was injected at the dose of 1.0 micrograms/100 g b.w. the MBC-T3nR was maintained within the normal range as long as 24 h after the injection (428 +/- 125 fmoles T3/mg protein) with serum T3 concentrations that were twice the normal levels (1.27 +/- 0.06 vs. 0.67 +/- 0.01 ng/ml). These results support the hypothesis that T3 modulates the concentration of its own nuclear receptors in the rat pituitary gland. The absence of any effect of T3 10 min after injection is suggestive of an effect of T3 on the synthesis of its receptors rather than on an alteration of unoccupied receptors that would require T3 for adequate configuration and detection. This modulation of pituitary T3 receptors by T3 may provide an additional mechanism of regulation of TSH secretion in thyroid insufficiency.
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PMID:Modulation of thyroid hormone nuclear receptor levels by L-triiodothyronine (T3) in the rat pituitary. 631 85

Ten patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled verapamil (estimated dose 3 mg) and sodium cromoglycate (estimated dose 12 mg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after running on a treadmill for eight minutes. There was no significant change in baseline FEV1 values after each agent. In the exercise periods, however, FEV1 fell by 45.4% (SEM 4.0) after saline inhalation, 18.4% (5.1) after sodium cromoglycate, and 16.7% (4.3) after verapamil. The inhibitory effects of sodium cromoglycate and verapamil were comparable and significantly different from saline (p less than 0.02 and p less than 0.01 respectively). Nevertheless, considerable intrasubject variability was observed. The findings suggest that mediator release, which is calcium dependent, may play an important part in exercise-induced asthma, and calcium antagonists may inhibit post-exercise bronchoconstriction by their blocking effect on calcium channels.
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PMID:Calcium antagonists in exercise-induced asthma. 678 57

Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate in increasing concentrations from 2 to 40 mg/ml. Saline was used as a control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after the patients had run on a treadmill for eight minutes. There was slight bronchodilation evident from the increase in baseline FEV1 after inhalation of sodium cromoglycate, the difference reaching statistical significance with the highest concentration (5.7%, p less than 0.05). After exercise the maximal percentage falls in FEV1 (means and SEM) after saline and after sodium cromoglycate at 2, 10, 20, and 40 mg/ml were 37.3 +/- 4.7, 17.3 +/- 4.1, 10 +/- 3.3, 7.6 +/- 2.4, and 12 +/- 2.9. Sodium cromoglycate inhibited the exercise-induced fall in FEV1 at all the concentrations used in the study (p less than 0.001) and its inhibitory effect increased from 2 to 20 mg/ml. The mean FEV1 returned to baseline values within 15 minutes at higher concentrations of sodium cromoglycate (20 and 40 mg/ml) and a small bronchodilator effect was noted at 30 minutes. The findings suggest that the protective effect of sodium cromoglycate in exercise asthma is dose related. At higher concentration the drug suppresses chemical mediator release from the lung mast cells and may also modify the bronchial reactivity to release mediators.
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PMID:Dose-response study of sodium cromoglycate in exercise-induced asthma. 681 7

Human and guinea-pig placental activity was measured in tissue extracts and in medium in which tissue fragments have been incubated. Lipase activity was estimated from measured rates of release of 3H-labelled fatty acids from a 3H-labelled triacylglycerol substrate. Whole tissue lipase activity was 1.6 +/- 0.3 units/g (mean +/- SEM, mumol of unesterified fatty acid release/min) in the human, and 87.1 +/- 7.3 units/g in guinea-pig placental tissue. 70% of the human and 56% of the guinea-pig placental activity was lost on treating the tissues with cold acetone. Sodium chloride (0.75 M) decreased activity by 50% in extracts from both species. Lipase activity was released into media when placental fragments were incubated. The addition of heparin increased the release of lipase from human placenta but not significantly from that of the guniea-pig. Insulin had no effect on placental lipase activity from either species. It is concluded that the placentas of both species contain at least two lipases. One of these, which constituted a large of the total, had the characteristics of lipoprotein lipase.
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PMID:Lipoprotein lipase activity in human and guinea-pig placenta. 714 75

Enkephalins inhibit guinea pig ileum contractions in vitro; in vivo they increase gastric contraction strength and small intestinal spike activity in dogs and stimulate tonic and phasic contractile activity of the human colon. This study investigated the question as to whether the stimulatory effect of the synthetic met-enkephalin analogue FK 33-824 on the human colon is antagonized by the narcotic antagonist naloxone. On 3 experimental days 12 healthy young males received in random order (a) 4 mg (subjects 1-6) or 10 mg (subjects 7-12) naloxone i.v. followed by 1 mg FK 33-824 i.m., (b) saline i.v. followed by 1 mg FK 33-824 i.m. and (c) saline i.v. followed by saline i.m. FK 33-824 following saline produced a rapid increase of tonic intraluminal pressure (mean increase: 9.9 +/- 2.5 SEM mmHg; P less than 0.001), an increase in contractions from 1.6 +/- 0.4 to 3.3 +/- 0.8 per min (P less than 0.001), a shift in the dominant frequency of rhythmic contractions from 1.0 +/- 2.5 to 2.5-3.5 cycles per min, an increase in the amplitude of contractions from 10.1 +/-0 2.1 to 15.0 +/- 3.2 mmHg (P less than 0.01), and in the sum of the amplitudes as an overall measure of contractile activity from 148.6 +/- 36.7 to 482.9 +/- 136.9 mmHg (P less than 0.01). All effects lasted for more than 70 min; peak changes occurred in the first 15 min and subsided slowly in intensity. The effects of FK 33-284 were greatly attenuated by premedication of 4 mg naloxone, and abolished, at least for 15-30 min, by 10 mg naloxone. Saline caused no changes. It is concluded that the stimulatory effects of FK 33-824 on human colonic motility are antagonized by naloxone.
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PMID:Stimulatory effects of the synthetic enkephalin analogue FK 33-824 on colonic motor activity antagonized by naloxone. 721 44

We wished to determine, using a novel specific antagonist of BK2, HOE 140, (a) if the angiotensin-converting enzyme (ACE) inhibitor, ramiprilat, reduces myocardial infarct size in a well-established animal model of ischemia/reperfusion with minimal coronary collateralization, and (b) if the reduction in myocardial infarct size occurred through a bradykinin-dependent mechanism Saline vehicle, ramiprilat, HOE 140, or ramiprilat plus HOE 140 (n = 6 each group), was administered intravenously (i.v.) in intact animal preparations of experimentally induced acute myocardial ischemia. Anesthetized, open-chest rabbits were instrumented for measurement of systemic hemodynamics and left ventricular pressure (LVP), from which LV + dP/dtmax was derived. Animals were subjected to 30-min left main coronary artery occlusion (marginal branch) followed by 2-h reperfusion. Ramiprilat (50 micrograms/kg) or saline was administered before reperfusion, and rabbits receiving HOE 140 were pretreated before occlusion (1 microgram/kg). In separate duration of action experiments (n = 6 each group), the above doses of ramiprilat or HOE 140 had significant vascular antagonism of sufficient duration against serial challenge with angiotensin I (AI) or bradykinin, respectively. After reperfusion, myocardial infarct size (IS) was determined by tetrazolium staining and expressed as a percentage of area at risk (AR). IS/AR% was significantly reduced in rabbits that received ramiprilat (20 +/- 6%, p < 0.05) as compared with those that received saline (41 +/- 6%), ramiprilat plus HOE 140 (47 +/- 2%), or HOE 140 alone (43 +/- 4%, mean +/- SEM). AR as a percentage of total LV mass was not different between any of the four treatment groups. Tachycardia was observed during early reperfusion in each group treated with ramiprilat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of myocardial infarct size in rabbits by ramiprilat: reversal by the bradykinin antagonist HOE 140. 768 28

Our objective in these experiments was to evaluate the effects of atrial natriuretic factor on the gain of the spontaneous baroreceptor-heart rate reflex in humans. On two separate study days, we gave either atrial natriuretic factor during supine rest (16 nmol over 3 minutes, then 16 pmol/kg per minute) or saline (as vehicle) to nine healthy men (age, 23 +/- 1 years; mean +/- SEM) according to a random, double-blind design. Beat-by-beat RR interval and systolic pressure were recorded noninvasively. Sequences during which systolic pressure and the RR interval of the following beat changed in parallel (either increasing [Up] or decreasing [Down]) over at least three consecutive beats were identified and classified as baroreceptor-heart rate reflex sequences. Regression lines relating RR interval to the preceding systolic pressure were derived for each individual sequence. The mean value of the slopes of these regression lines was calculated to obtain the mean spontaneous baroreflex sensitivity for heart rate for each subject. Saline infusion did not change RR interval, systolic pressure, or number of baroreflex sequences nor the slope of the mean spontaneous baroreflex sensitivity for heart rate or slopes of Up or Down sequences. Atrial natriuretic factor, at a dose that lowers central venous pressure, did not affect systolic pressure, respiratory rate, or the number of baroreflex sequences but reduced RR interval from 952 +/- 35 to 930 +/- 40 ms (P < .04) and the mean slope of spontaneous baroreflex sensitivity for heart rate from 32.7 +/- 4.8 to 23.1 +/- 2.8 ms.mm Hg-1 (P < .04).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of atrial natriuretic factor on spontaneous baroreflex sensitivity for heart rate in humans. 776 58

Eight dogs (body weight, 12.5 to 21.5 kg) were assigned at random to each of 3 treatment groups (IS, IX, IM) that were not given glycopyrrolate and to each of 3 groups that were given glycopyrrolate (IGS, IGX, IGM). Dogs were anesthetized with isoflurane (1.95% end-tidal concentration), and ventilation was controlled (PCO2, 35 to 40 mm of Hg end-tidal concentration). Glycopyrrolate was administered IV and IM at a dosage of 11 micrograms/kg of body weight, each. Saline solution, xylazine (1.1 mg/kg, IM), or medetomidine (15 micrograms/kg, IM) was administered 10 minutes after baseline ADE determination. Redetermination of the ADE at the same infusion rate was started 10 minutes after drug administration. Arrhythmogenic dose was determined by constant infusion of epinephrine at rates of 1.0, 2.5, and 5.0 micrograms/kg/min. The ADE was defined as the total dose of epinephrine that induced at least 4 ectopic ventricular depolarizations within 15 seconds during a 3-minute infusion, or within 1 minute after the end of the infusion. Total dose was calculated as the product of infusion rate and time to arrhythmia. Statistical analysis of the differences between baseline and treatment ADE values was performed by use of one-way ANOVA. Mean +/- SEM baseline ADE values for groups IS, IX, and IM were 1.55 +/- 0.23, 1.61 +/- 0.28, and 1.95 +/- 0.65 micrograms/kg, respectively. Differences for groups IS, IX, and IM were -0.12 +/- 0.05, -0.31 +/- 0.40, and -0.17 +/- 0.26, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in the arrhythmogenic dose of epinephrine after xylazine or medetomidine administration in isoflurane-anesthetized dogs. 790 30

The aim of this study was to investigate whether, when muscle glycogen is reduced, a pre-exercise infusion of branched-chain amino acids (BCAA) modifies exercise performance or the metabolic and respiratory responses to incremental exercise. Six moderately trained volunteers took part in the following protocol on two occasions. On day 1, at 9 a.m. in the postabsorptive state, they performed a graded incremental exercise (increases of 35 W every 4 min) to exhaustion (Ex-1). A meal of 1,000 kcal (4,200 kJ; 60% protein, 40% fat) was consumed at 12 p.m. No food was then allowed until the end of the experiment (20-21 h later). A 90-min period of exercise at alternating high and moderate intensities, designed to deplete muscle glycogen, was performed between 6 p.m. and 7.30 p.m. The morning after (day 2), the subjects randomly received either a mixed solution of BCAA (260 mg x kg-1 x h-1 for 70 min), or saline. They then repeated the graded incremental exercise to exhaustion (Ex-2). Metabolic and respiratory measurements suggested a muscle glycogen-depleted state had been achieved. No significant differences were observed in total work performed, maximal oxygen uptake or plasma ammonia, alanine, and blood pyruvate concentrations in the two treatments. After BCAA infusion, higher blood lactate concentrations were observed at maximal power output in comparison with those during saline [BCAA 4.97 (SEM 0.41) mmol x l-1, Saline 3.88 (SEM 0.47) mmol x l-1, P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of infusing branched-chain amino acid during incremental exercise with reduced muscle glycogen content. 795 52


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