摘要:

Environmental pollutants may induce airway hyperresponsiveness to bronchoconstrictor stimuli, but if there is a concomitant change in other defensive reflexes, like the cough reflex, is not known. We have examined how two weeks' exposure to cigarette smoke influences airway sensitivity to inhaled irritants acting mainly through capsaicin‐sensitive sensory neurons (citric acid, capsaicin) or rapidly adapting stretch receptors (cigarette smoke, histamine). Guinea‐pigs were exposed, over a period of one hour, to cigarette smoke or room air, twice daily for 2 weeks. Twenty‐four hours after the end of the smoke exposure coughing produced by nebulized citric acid (0.40 M) and capsaicin (30 μM) was enhanced 3.7 (P<0.001) and 2.S (P<0.05) times, respectively, whereas the cigarette smoke‐induced cough was unchanged. The enhanced responsiveness gradually returned to normal over a period of three weeks and was not mediated by cyclo‐oxygenase products since it was not affected by indomethacin (3 μmol kg‐1). In contrast, the broncho‐constrictor responses to citric acid, capsaicin, cigarette smoke and histamine (0.70 mM) were not altered by inhalation of cigarette smoke. Smoke‐exposed animals had a significantly (P<0.05) increased amount of calcitonin gene‐related peptide‐like material (CGRP, contained in capsaicin‐sensitive sensory neurons) in tracheal tissue, suggesting that chronic irritation stimulates peptide synthesis. The amount of neuropeptide Y‐like material (in autonomic motor nerves) in pulmonary tissue was not changed indicating some ‘specificity’ in the irritative effect of smoke. It is concluded that prolonged exposure to cigarette smoke produces a tussive hyperresponsiveness that seems to involve specifically capsaicin‐sensitive, CGRP‐containing sensory neurons mediating cough. The present data demonstrate the development of a ‘sensory’ hyperresponsiveness, separate from airway hyperrespon

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09105.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The effect of neuropeptide Y (NPY) on uveal vascular resistance was studied in rabbits by direct determination of uveal blood flow from a cannulated vortex vein. Regional blood flows, in the eye, the brain and several other tissues, were measured, with radioactive microspheres, during neuropeptide Y‐infusion in rabbits with and without α‐adrenoceptor blockade.Intravenous infusion of increasing doses of neuropeptide Y caused a dose‐dependent increase in the total uveal vascular resistance. Maximal effect, a 70% increase, was achieved with 120 pmol kg‐1min‐1. In the microsphere experiments, this dose rate was given i.v. over 10 minutes and blood flow determinations were made before and at 2 and 10 minutes after the start of the infusion. After 2 minutes of neuropeptide Y, there were marked blood flow reductions in the spleen, kidneys, adrenal glands, gastro‐intestinal tract, choroid plexus and pineal and pituitary gland. The effect in the eye was small at 2 minutes, but at 10 minutes local blood flows in the choroid and the ciliary body were decreased by 50% and the iridal blood flow by 30%. Retinal blood flow was not affected by neuropeptide Y. At 10 minutes there were also significant blood flow reductions in the brain, tongue, masseter muscle and several glandular tissues. The effects of neuropeptide Y on local blood flow in rabbits that had been subjected to α‐adrenoceptor blockade were very similar to the effects in the animals without α‐adrenoceptor blockade.The results show that, in the rabbit, neuropeptide Y has marked effects on local blood flows in several tissues, including the eye, and suggest that neuropeptide Y may significantly contribute to the uveal vasoconstriction during sympathetic

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09106.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Monoclonal antibodies to the axonal transport ATPase kinesin were used in an immunofluorescent study on mammalian nerves. Following crushing of the sciatic nerve and the ventral roots of adult rats, immunoreactive material was found to accumulate rapidly, mainly proximal to a crush but also, to some degree, distal to a crush. The strongest immunofluorescence was observed after incubation with the H2 antibody against the heavy subunit of kinesin. Using the cytofluorimetric scanning (CFS) procedure, the accumulated amounts were quantified and it was found that the retrogradely accumulating kinesin‐like immunoreactivity (IR) was about 4–12% of the anterogradely transported kinesin‐IR. The results were compared to the vesicle marker p38 (synaptophysin), which was found to accumulate to a significant extent on both sides of the crush. Cytofluorimetric scanning measurements indicated that nearly 50% of the anterogradely accumulated p38–IR was recycling to the cell body. The results demonstrate that kinesin in the living axon is affiliated with anterogradely transported organelles. Retrogradely transported organelles appeared to carry very little kinesin‐IR, suggesting that kinesin may be subject to turnover, distinct from that of p38, in the distal regions of

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09107.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10‐7–10‐9M, inhibited, while at 10‐12–10‐14M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10‐6–10‐9M, a stimulation was found at 10‐13–10‐14M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C‐ and N‐terminal fragments, while a stimulating effect was retained in the N‐terminal fragment, at 10‐14M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin‐glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide see

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09108.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Ablation of renal tissue in infancy is followed by increased ultrafiltration pressure, enlarged filtering area and decreased hydraulic conductivity of the glomerular capillaries. This study examines the effect of a calcium channel blocker, felodipine, on ultrafiltration pressure and renal function in rats uni‐nephrectomized at 5 days of age. The rats were treated with felodipine from 24 to 60 days of age or left untreated. Sham‐operated untreated rats were used as controls. Arterial blood pressure levels were similar in the three groups of rats. Glomerular filtration rate and renal plasma flow in the left kidney were significantly higher in treated and untreated rats than in sham‐operated untreated rats; significantly higher values were also found in treated than in untreated rats. Single nephron glomerular filtration rate was significantly higher in treated and in untreated than in sham‐operated untreated rats, but was not different in treated and untreated rats. Ultrafiltration pressure was significantly higher in untreated rats than in treated and in sham‐operated untreated rats; no difference was found between treated and sham‐operated untreated rats. Ultrafiltration coefficient (Kf) was significantly higher in treated rats than in untreated and sham‐operated untreated rats. Hydrolic conductivity of the glomerular capillaries was significantly lower in untreated than in treated and in sham‐operated rats, but was not different in treated and sham‐operated rats. Glomerular volume was higher in treated and untreated rats than in sham‐operated rats. Conclusion: high ultrafiltration pressure is not an absolute requirement for the hyperfiltration that follows

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09109.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The long‐term effect of elevated tail venous pressure (Pv) on interstitial fluid pressure (Pi) and colloid osmotic pressure (COPi) was studied in rats. Measurements were performed on different rats after 1–5 days of congestion, and on a sham operated control group. Two different degrees of venous stasis were obtained by means of graded ligation of tail veins and skin. Moderate degree of ligation (group 1) caused no visual oedema. More extensive ligation (group 2) gave marked oedema already on day 1 and further progression and exudation from the skin during the following 3 days. Tail venous pressure was measured by micropuncture and interstitial fluid pressure by the wick‐in‐needle technique. Interstitial fluid was sampled by a dry wick method, and colloid osmotic pressure was measured with a membrane osmometer.In group 1,Pvhad increased from 6.5 to 21.5 mmHg on day 1, and thereafter remained unchanged. Interstitial fluid pressure increased from 3.4 to 16.9 mmHg after ligation and to 19.2 mmHg on day 1. Colloid osmotic pressure fell from 11.7 to 5.8 mmHg. From day 1, both interstitial fluid pressure and colloid osmotic pressure remained largely unchanged.In group 2 rats, tail venous pressure increased to 33.0 and 36.3 mmHg on day 1 and 2 and then fell towards control level during the following 3 days. Interstitial fluid pressure increased to 22.9 and 31.4 mmHg before a rapid decline towards control level. Colloid osmotic pressure was reduced from 11.7 to 5.6 mmHg.We conclude that hydrostatic counterpressure may provide an oedema‐preventing effect of up to about 15 mmHg. Greater acute increase of interstitial fluid pressure lead to exudation and pressure fall. Reduction of colloid osmotic pressure contributed 6–7 mmHg alrea

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09110.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Previous studies of non‐uniform performance of a myocardial region have indicated that measurement of local contraction is vectorial. Myocardial performance in one direction mainly, but not exclusively, depends on performance of the wall fibres in this same direction irrespective of wall depth. In this study we therefore determined fibre direction across the anterior wall of the left ventricle in twelve cats. Based on the fibre configuration a simple model is developed to analyse and predict the degree of uniformity of contraction. Fibre direction shifted continuously across the wall, from almost alignment with global apex‐to‐base axis in the endocardium (90d̀), to close to the equatorial direction (0d̀) in the midwall, and finally to about ‐ 50d̀ in the epicardial layer. The model predicts less uniformity with reduction of preload, and in the event of subendocardial ischaemia, which fits well with experimental data. Analysis of uniformity based on the integrated vectorial contribution of all myocardial layers thus provides a way to quantify regional uniformity/non‐uniformity as a regulatory mechanism of card

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09111.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

We measured right ventricular coronary blood flow with radioactive microspheres during graded aortic pressure reduction in 13 normal dogs and in 13 renal hypertensive dogs with left ventricular hypertrophy. Under anaesthesia and controlled loading conditions, mean aortic pressure was lowered from control (128 mmHg in normal and 146 mmHg in hypertensive dogs) to approximately 100, 90 and 80 mmHg. In normal dogs, right ventricular blood flow was not affected by this pressure reduction, consistent with effective right ventricular autoregulation. In hypertensive dogs, however, right ventricular blood flow was maintained between a mean aortic pressure of 146 and 90 mmHg (range 75–79 ml min‐1100 g‐1) but fell by 18% to 63 ml min 100 g‐1at a mean aortic pressure of 80 mmHg (P<0.005). We conclude that autoregulation of right ventricular blood flow was preserved in chronic hypertension but that, compared to normal dogs, the lower limit of autoregulation was reset to a higher pressure level. Moreover, the similarity of right ventricular‐to‐body weight ratios in the two groups implied that this change was a consequence of hypertension‐induced structural changes in the coronar

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09112.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The kidneys have a humoral antihypertensive system, located in the renal medulla and presumably antagonizing the pro‐hypertensive renin‐angiotensin system. Medullipin I and II and maybe platelet activating factor (PAF), seem to be the mediators of this system, known to be activated after reversal of renovascular hypertension or when the perfusion pressure to a normotensive kidney is suddenly elevated.The present study was undertaken to investigate whether this system is functioning also in the spontaneously hypertensive rat (SHR), and if it is then reset in proportion to the increased mean arterial pressure (MAP). Isolated kidneys from spontaneously hypertensive rats and from Wistar Kyoto rats (WKY) were cross‐perfused in vivo from anaesthetized intact Wistar Kyoto rat ‘donors’. After 30 min of perfusion at 100 mmHg the perfusion pressure to the isolated kidneys were, for 60 min, either kept unaltered at 100 mmHg or, for the Wistar Kyoto rat kidneys, increased to 150–200 mmHg and, for the spontaneously hypertensive rat kidneys, raised to 200 or 250 mmHg.The results show that the humoral antihypertensive system is present also in spontaneously hypertensive rat kidneys, but is here reset upwards to or even beyond the elevated MAP level. Furthermore, all mean arterial pressure reductions caused by high‐pressure perfusion of Wistar Kyoto and spontaneously hypertensive rat kidneys were accompanied by reductions in heart rate (HR) in the ‘donors’, in agreement with previous observations after reversing renal hypertension and after i.v. medullipin I injection.In fact, in spontaneously hypertensive rat kidneys, the ‘incretory’ depressor mechanism appears to be more markedly reset upwards than is the ‘excretory’ depressor mechanism inherent in pressure diuresis with consequent salt‐volume elimination.In conclusion spontaneously hypertensive rats, like Wistar Kyoto rats and Wistar rats, have a humoral antihypertensive system in the kidneys, but it is reset upwards even beyond the elevated mean arterial pressure level in spontaneously hypertensive rats. The combination of a depressor response and reduced heart rate in the ‘donors’ renders further evidence that the medullipins are the principal, though probably not the only, humoral antihypertensive factors released fr

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09113.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Isolated smooth muscle preparations from the sheep urethra responded to electrical field stimulation with contraction when basal tension was low (5–6 mN), but with relaxation when the preparations were contracted with noradrenaline (NA), clonidine, or prostaglandin F2α. No relaxant response could be elicited in high K+ (124 mM) contracted preparations. Electrically induced relaxations had a threshold of less than 1 Hz and a maximum at 8 Hz. Both contractant and relaxant responses were abolished by tetrodotoxin, indicating that they were caused by transmitters released from nerves.The amplitude of the relaxant responses showed a highly significant correlation to the tension induced by noradrenaline. A coefficient (R/T) was calculated relating relaxation to noradrenaline‐induced tension. In this way it is possible to separate the effect of drugs on muscle tension (non‐specific effect) from their action on the electrically induced relaxation (specific effect). Chemical sympathectomy with 6‐OHDA did not significantly modify the relaxant response to 6 Hz in noradrenaline contracted strips, as evaluated by the R/T coefficient. The electrically induced relaxation was not affected by hexamethonium, propranolol, phentolamine, muscarinic receptor blockade, cocaine, indomethacin, or methysergide. Both nifedipine and Bay K 8644 inhibited significantly the response induced by electrical stimulation, decreasing its maximum. Nifedipine, but not Bay K 8644, significantly reduced the level of tension induced by noradrenaline, and its effect, evaluated by the R/T coefficient, was an increase in the electrically induced relaxation, whereas Bay K 8644 had a significant inhibitory effect. Pre‐treatment with NG‐nitro‐L‐arginine (L‐NOARG) for 30 minutes did not significantly change resting tension, but concentration‐dependently reduced the relaxant responses, and at the highest L‐NOARG concentration used, relaxation was changed into a contraction. NO (present in acidified solution of NaNO2) still produced relaxation. NG‐nitro‐D‐arginine (D‐NOARG) had no effects.It is suggested that in contracted sheep urethral muscle, the relaxation produced by electrical stimulati

ISSN:0001-6772    

DOI:10.1111/j.1748-1716.1991.tb09114.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY