摘要:

Six alloxan-diabetic dogs with fasting plasma glucose levels above 200 mg/100 mL were treated with rectal administration of insulin suppositories twice a day for 6–9 days. The effectiveness was compared with that of subcutaneous insulin injections. In three diabetic dogs with fasting plasma glucose levels below 300 mg/100 mL, both insulin suppository at a dose of 20 U (2.3 U/kg) and subcutaneous insulin at a dose of 0.2 U/kg showed a similar effect in reducing fasting glucose levels and daily urinary glucose amounts. In dogs with higher fasting glucose levels, 0.5 U of subcutaneous insulin/kg is less effective in reducing fasting glucose than 50 U (5.2 U/kg) suppositories, in spite of the same effects on daily urinary glucose output. Postprandial glucose responses were significantly lessened with rectal administration of insulin suppositories. The integrated area of increase in peripheral insulin concentration after subcutaneous injection of 0.2 or 0.5 U insulin/kg was significantly greater than that after rectal administration of an insulin suppository (2.3 or 5.2 U/kg, respectively). These results indicate that diabetes could be controlled by the daily rectal administration of an insulin suppository instead of the conventional subcutaneous injection.

ISSN:0008-4212    

DOI:10.1139/y81-001

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

Chloride current–voltage relations inXenopus laevismuscle membrane have been investigated in phosphate-buffered solution (pH 5.2–5.4) using a three-microelectrode voltage clamp. Resting chloride conductance in these conditions is about 10−4 S/cm2, approximatelyth that at pH 8.8. When the membrane potential is stepped from the holding (resting) potential to a more negative voltage the current rises from the initial to the steady state. The instantaneous current–voltage relation is linear and the steady-state relation shows inward-going rectification. As hyperpolarization appears to "activate" the chloride conductance, the "availability" of chloride current has been measured at the beginning of a voltage step to a standard test potential following conditioning at a variety of potentials. The relationship between the test current and the conditioning voltage is sigmoid. The normalized sigmoid curve has the same slope (absolute value) but opposite sign to that obtained in the same experiment at pH 8.8. In mildly acidic solutions (pH 6.4) the current wave form is diphasic: current initially falls then rises to the steady state. This combination of transients militates against the idea that transients are due solely to accumulation–depletion effects in restricted spaces ("unstirred layers") and a hypothesis is qualitatively outlined in which pH- and voltage-dependent effects are ascribed to a single type of channel whose orientation in the membrane is unconstrained.

ISSN:0008-4212    

DOI:10.1139/y81-002

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

The effects of selective histamine receptor analogs were studied in spontaneously beating rabbit atria. Atrial rate was increased by histamine (an H1and H2agonist), 4-methylhistamine and impromidine (H2agonists), and 2-pyridylethylamine (PEA, an H1agonist). The responses to histamine, 4-methylhistamine, and impromidine were not affected by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the response to PEA was nearly abolished upon pretreatment with propranolol or reserpine.Cimetidine pretreatment (H2receptor blockade) competitively antagonised the positive chronotropic effects of histamine, 4-methylhistamine, and impromidine. Promethazine pretreatment (H1receptor blockade) competitively blocked the chronotropic effects of histamine but had no effect on the responses to 4-methylhistamine or impromidine. These results suggest that stimulation of H1and H2receptors will cause a positive chronotropic response.

ISSN:0008-4212    

DOI:10.1139/y81-003

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

The effects of selective histamine receptor analogs were studied in electrically paced rabbit left atria. Atrial tension was increased by histamine (an H1and H2agonist), 4-methylhistamine and impromidine (H2agonists), and 2-pyridylethylamine (PEA) (an H1agonist). The responses to histamine and impromidine were not altered by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the responses to 4-methylhistamine and PEA were significantly decreased upon pretreatment with propranolol or reserpine. Promethazine pretreatment (H1receptor blockade) antagonized the inotropic effects of histamine and PEA but had no effect on the responses to 4-methylhistamine or impromidine. Cimetidine pretreatment (H2receptor antagonism) competitively blocked the positive inotropic effects of histamine, 4-methylhistamine, and impromidine. These results suggest that the left atrial inotropic response is mediated through H1and H2receptor stimulation.

ISSN:0008-4212    

DOI:10.1139/y81-004

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

Rabbit isolated right and left atria were exposed to theophylline and to selected doses of histamine agonists. Right atrial rate and left atrial tension were increased by theophylline (3 × 10−4 M), the H1agonist 2-pyridylethylamine (PEA) (1 × 10−4 M), and the H2agonists 4-methylhistamine (1 × 10−4 M) and impromidine (1 × 10−8 M). In the right atria the combined effect of theophylline (3 × 10−4 M) and any of the histamine agonists was greater than the response to either agonist alone. However, the combined effects were not significantly greater than the sum of the individual right atrial responses. In the left atria the combined effect of theophylline (3 × 10−4 M) with any one of the histamine agonists was not only greater than the response to either agonist alone but was also significantly greater than the sum of the individual responses. The potentiation of the left atrial response to the H2agonists by theophylline was significantly decreased by the H2antagonist cimetidine (1 × 10−5 M). However, the potentiation of the left atrial response to the H1agonist (PEA) by theophylline was not significantly altered by the H1antagonist promethazine (2 × 10−6 M). Reports that the cardiac effects of H1and H2receptor agonists are potentiated by phosphodiesterase inhibitors such as theophylline as a result of increased cyclic AMP levels are not supported by the present study.

ISSN:0008-4212    

DOI:10.1139/y81-005

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

Proteins labeled with [35S] methionine or [3H]leucine were generatedin vitroin bullfrog dorsal root ganglia and their fast axonal transport in the spinal nerves was followed during a subsequent incubation period. Incubation of the ganglia in a medium where sucrose, choline chloride, or sodium isethionate replaced NaCl caused respectively an 88, a 37, or a 76% reduction in the quantity of proteins carried by the fast axonal transport system; no decrease in synthesis of labeled proteins was observed and protein transport followed the usual time course. Incubation of desheathed spinal nerves in a medium where sucrose replaced NaCl reduced by 67% the quantity of labeled proteins which were transported past the desheathed region. Although both the axons and the dorsal root ganglia exhibit the requirement for monovalent ions to maintain fast axonal transport, the possibility that the ionic requirements of the ganglia pertain to the somal portion of the nerve cell is discussed.

ISSN:0008-4212    

DOI:10.1139/y81-006

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

Intravenously administered cyclobenzaprine (CBZ) (Flexeril), a clinically used, centrally acting muscle relaxant, abolished muscle rigidity in the intercollicular decerebrate rat. In animals in which the locus coeruleus was lesioned bilaterally previously, CBZ failed to attenuate the electromyogram. In the ventral horn of the cord, which receives a dense noradrenergic innervation from the locus coeruleus, CBZ caused an increase in the metabolism of noradrenaline. In the zona intermedia of the thoracic cord, which is not innervated by the locus coeruleus, CBZ caused only minimal effects on noradrenaline metabolism. Cells in the locus coeruleus were activated by CBZ. The results indicate that in the intercollicular decerebrate rat, an intact, coerulospinal, noradrenergic projection is essential for the muscle relaxant effect of CBZ. Muscle relaxation apparently results from an activation of locus coeruleus neurones, leading to an increased release of noradrenaline in the ventral horn of the cord and the subsequent inhibitory action of noradrenaline on α motoneurones.

ISSN:0008-4212    

DOI:10.1139/y81-007

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

The mechanism for the reduction of both systemic arterial blood pressure and cardiac output (CO) and for the elevation of intravascular pressure which accompanies positive end-expiratory pressure ventilation (PEEP) remains uncertain. The role of the intact pericardium and the chest wall has not been defined. This study examines cardiac transmural pressure with PEEP (0, 4, 8, and 16 cm H2O) administration in nine closed chest, anesthetized, normovolemic dogs utilizing direct measurements of intrapericardial pressure. The experiment was repeated following pericardiectomy and left thoracotomy. The closed chest dogs exhibited significant reductions in blood pressure and CO without detectable changes in transmural pressure. With combined pericardiectomy and left thoracotomy, the responses of both CO and blood pressure to PEEP were similar to those observed with the chest closed. Absolute right atrial pressures were similar at all levels of PEEP and were independent of the presence of the pericardium and the intact chest wall. The rise in absolute left atrial pressure observed with these structures intact was completely abolished by pericardiectomy and left thoracotomy. Thus the major hemodynamic effects of PEEP, namely changes in blood pressure and CO, cannot be accounted for by changes in transmural pressure or influences from the intact chest wall and pericardium.

ISSN:0008-4212    

DOI:10.1139/y81-008

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

Nine-tenths of the inflowing blood passes through the normal relaxed spleen via a fast arteriovenous pathway whereas the remainder travels slowly via the red pulp. However, flow through this fast pathway diminishes to zero when the organ is distended by perfusion at high venous pressure. The present investigation, in which a slug-injection procedure was used to determine the volumes of distribution of red cells and125I-labelled albumin in isolated, Ringer-perfused cat spleens during a single transit, has shown that in spleens contracted by noradrenaline the entire inflow passes via the fast arteriovenous pathway. The peak outflow concentration of125I-labelled albumin occurred much later (factor 2.03) than that of red cells. This difference is too great to be accounted for solely by axial accumulation of red cells within a closed system of vessels in vivo and indicates that albumin was distributed throughout a significantly larger space than red cells. These findings are explained in terms of the classical observations of MacKenzie and co-workers on red cell movement in transilluminated mouse spleens during contraction. Whether the splenic retention of damaged red cells would change as a result of the altered flow pathways is not yet known.

ISSN:0008-4212    

DOI:10.1139/y81-009

出版商:NRC Research Press    

年代:1981

数据来源: NRC

摘要:

The effect of acute or chronic renal denervation, furosemide, or acute saline loading on the postobstructive diuresis (POD) which occurs after relief of 24-h bilateral ureteral obstruction (BUO) was studied in anaesthetized rats. Acute renal denervation during POD 1–2 h after relief of BUO had no effect on glomerular filtration rate or sodium, potassium, water, or solute excretion, in contrast with its natriuretic and diuretic effect in sham-operated rats. Intravenous furosemide or acute saline loading caused a further marked increase in sodium and water excretion during POD, demonstrating the ability of the kidney undergoing POD to respond to other types of natriuretic stimuli. Chronic renal denervation prior to BUO had no effect on subsequent POD.The lack of response of the BUO kidney undergoing POD to acute denervation contrasts with the changes in renal function following denervation of the unilateral postobstructive kidney. The results indicate that the kidney undergoing POD after relief of BUO may be functionally denervated and suggest that inhibition of renal nerve activity could contribute to the pathophysiology of POD.

ISSN:0008-4212    

DOI:10.1139/y81-010

出版商:NRC Research Press    

年代:1981

数据来源: NRC