Quarterly journal of experimental physiology (Cambridge, England)最新文献

In dogs anaesthetized with chloralose, cardiac receptors were stimulated by increases in left ventricular systolic pressure effected by changes in aortic root pressure. Left atrial and carotid sinus pressures were controlled. A large step increase in ventricular pressure resulted in transient decreases in heart rate, systemic arterial perfusion pressure and perfusion pressure to a vascularly isolated hind limb. The magnitudes of these responses were about three-quarters of those to either a large change in carotid sinus pressure or aortic root injection of 20 micrograms veratridine. Steady-state responses were smaller. There was no significant change in perfusion pressure to a perfused cutaneous vein. Graded changes in ventricular systolic pressure showed that the most sensitive pressure range was between 20 and 24 kPa. These results indicate that changes in left ventricular pressure result in significant vasodilation in the hind limb and in other regions and that responses are obtained when the pressure is moderately elevated.

The development and involution of mouse mammary tissue was measured in terms of changes in the cell population and the synthetic capacity of cells during the course of pregnancy, lactation and natural weaning, and after lactation was extended by introduction of foster litters of younger pups. Synthetic capacity was assessed by measuring the activities of several key enzymes closely concerned with the synthesis of milk constituents together with other constitutive enzymes. The capacity of the tissue to synthesize lactose and casein was also measured using short-term cultures of freshly prepared mammary explants. Results showed that the mammary cell population began to increase and differentiate around the time of parturition. Cell numbers increased up to day 5 of lactation, whereas cellular differentiation continued through lactation until day 15, around the time of peak milk yield. After day 15 there was a sharp drop, followed by a gradual decline in synthetic capacity and cell population, as pups were weaned. Substitution of younger pups for the natural litter at day 15 prevented the normal fall in milk secretion. In this case, mammary cell number remained at day 15 levels; cellular differentiation was also maintained to a considerable degree, although several markers of differentiation decreased during extended lactation.

The effect of increasing heart rate by increasing the rate of atrial pacing in the absence of any reflex effects from atrial receptors, by cooling the vagi to 12 degrees C, was studied in two groups of dogs with different blood volumes. In one group of nine dogs with a high blood volume increasing heart rate, by an amount similar to that reflexly obtained in response to stimulation of atrial receptors, resulted in significant increases in urine flow and sodium excretion; in another group of eight dogs with a low blood volume similar increases in heart rate did not result in a diuresis or natriuresis. The findings suggest that the effects of an increase in heart rate in combination with differences in blood volume could contribute to the previously reported differences in the urinary responses that result from stimulation of atrial receptors in dogs with different blood volumes.

Carbimazole (100 mg/kg diet) was fed to pullets from 8 to 12 or from 12 to 16 weeks of age. Pullets fed carbimazole from 8 to 12 weeks of age matured about 12 d earlier and produced more eggs between 17 and 22 weeks of age. Their body weights and feed intake were significantly lower than those of normal birds. Feeding carbimazole from 12 to 16 weeks of age had no significant effect on the birds except during the course of treatment where their feed consumption was less than that of the controls.

Ewes carrying twin fetuses were maintained during late pregnancy on a uniformly high plane (well fed), a uniformly low plane (underfed) or a low plane rising to a high plane (refed) of nutrition. The maternal plasma concentrations of hormones concerned with udder development, colostrum production and milk secretion were measured in samples obtained during the last 32 d before and the first 18 h after birth. Udder weights were derived from their linear dimensions, the yields of mammary secretions by hand milking during the first 18 h after birth and the transition from colostrum to milk was indicated by changes in the concentrations of lactose, lipid and immunoglobulin G. Underfeeding reduced prenatal udder development and colostrum accumulation and delayed the post-natal transition to milk secretion. Refeeding previously underfed ewes to a high plane during the last 5 d before birth had no effect on udder growth, but it did return the secretory functions of udder tissue to the levels observed in well-fed ewes. Nutritional effects on the plasma concentrations of insulin, placental lactogen, prolactin, cortisol and oestradiol-17 beta were small or absent. The relative changes in the plasma concentrations of growth hormone and insulin were such that the growth hormone: insulin ratio increased markedly during the last 11 d before birth in the underfed and refed ewes but not in the well-fed ewes. These differences in the growth hormone: insulin ratio were associated with greater increases in udder growth rate in the underfed and refed ewes than in the well-fed ewes. The plasma concentrations of progesterone decreased before birth in all ewes, but the decrease was delayed by underfeeding and refeeding rapidly overcame this effect. The slower progesterone withdrawal in the underfed ewes was associated with a delay in lactogenesis. It is concluded that the nutritionally induced changes in the growth hormone: insulin ratio and in the progesterone concentrations were the most likely endocrine determinants of the observed differences in the rates of mammogenesis and lactogenesis, respectively, but possible independent effects of substrate supply to the udder remain to be clarified.

The 3H-labelled loop diuretic bumetanide has been used to investigate loop diuretic binding to purified plasma membranes from rabbit kidney cortex (and outer medulla). Bumetanide binding to partially purified cortical plasma membranes in the range 0-10 microM, in a buffer containing principally Na, K and Cl ions, consists of a linear non-saturable component as assessed by 100 microM unlabelled bumetanide, and a saturable component consisting of high- and low-affinity binding sites, half-maximal binding being observed at 1.3 and 220 microM, respectively. The high-affinity site was found to be present in a fraction enriched in basolateral membrane markers when plasma membranes were further purified on a continuous Percoll gradient, whilst bumetanide binding to fractions enriched in brush-border or mitochondrial membrane markers was of lower affinity. Several features of bumetanide binding to basolateral membrane marker-enriched fractions are consistent with binding to the Na+K+Cl 'co-transporter' inhibited by loop diuretics: half-maximal binding was observed at 1.8 microM, with a finite maximal binding capacity of 78 pmol/mg. The relative efficacy of several loop diuretics for displacement of [3H]bumetanide was bumetanide greater than piretanide greater than furosemide = ethacrynic acid. Binding of loop diuretic was found to be dependent upon the medium ionic composition, Na, K and Cl being required to give maximal binding. The ability of probenecid and 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS) to compete with [3H]bumetanide was tested since these compounds are known inhibitors of anion secretion in the proximal nephron. Both DIDS and probenecid were able to effectively compete with [3H]bumetanide binding. A test of the ability of these compounds to inhibit 'co-transport' flux was made in intact MDCK cells using the ouabain-insensitive 86Rb (K) influx. Probenecid, at the concentrations seen to displace [3H]bumetanide binding to renal plasma membranes, was an effective inhibitor of 'co-transport' whereas DIDS was not. The adequacy of present criteria as to the identification of the 'co-transporter' in renal membranes using [3H]bumetanide binding are discussed in the light of this evidence.

Thirty broilers 8-10 weeks old were used to study the rate of food passage in chickens. Wheat bran and rice husks of three different sizes: more than 2 mm, between 1 and 1.5 mm, and less than 0.5 mm, mordanted with chromium, were used as markers. The suitability of these markers to study the rate of food passage in chickens and the possible influence of the size and hardness of the particle on the retention time was the objective of this study. Both T1, the time of first appearance of the marker, and Tm, the mean retention time, have been evaluated. Tm was a better parameter than T1 for studying transit time. Tm was longer with the biggest particles, especially with rice husk. The gizzard, with its grinding activity and pylorus, a selector of particle size, seems to be the transit regulator for solid particles in chickens. No chromium was found in the caecal contents of any case.

In man, parotid flow has been recorded bilaterally using modified Lashley cups in response to mechanical stimulation of the teeth. The stimulus was defined and controlled by monitoring the rectified and integrated masseter electromyographic activity (e.m.g.) during repeated clenching on closely fitting bite-blocks placed between the molar teeth. Unilateral clenching on a bite-block resulted in a greater flow from the ipsilateral than the contralateral gland, and both exceeded the control values. There was also a positive correlation between the masseter e.m.g. activity and ipsilateral parotid flow. Parotid flow was also recorded before and during local anaesthesia of various intra-oral branches of the trigeminal nerve. Anaesthesia of two to three inputs always produced significant reductions in ipsilateral flow, but anaesthesia of a single input was not always effective. These results provide evidence in support of the hypothesis that intra-oral mechanoreceptors, particularly periodontal mechanoreceptors, are involved in the masticatory-salivary reflex.

Glandular kallikrein has been assessed in submandibular saliva, homogenates and plasma by the fluorimetric substrate D-Val-Leu-Arg-7-amino-4-trifluoromethylcoumarin (AFC) and histochemically in tissue sections by the 4-methoxy-2-naphthylamide (MNA) analogue. Nerve stimulation was used to produce salivary secretion. Parasympathetic saliva contained low concentrations of kallikrein, independently of any circulating catecholamines from the adrenals. Sympathetic saliva contained very high concentrations of kallikrein; the amounts in individual drops rapidly reached a peak then declined gradually. Adrenergic blocking drugs during mixed parasympathetic and sympathetic stimulation showed that beta-adrenergic effects normally increase the secretion of kallikrein in response to the alpha-adrenergic influence from sympathetic nerve impulses. Small amounts of a glandular kallikrein-like activity are present in the plasma. Effluent blood from the submandibular gland before, during and after stimulation of either nerve gave no indication that submandibular kallikrein passes from the glandular compartment to the blood under conditions of unobstructed salivary flow. Excision of the chorda tympani indicated that parasympathetic nerve impulses are required for the normal resynthesis of submandibular kallikrein. The secretion of salivary kallikrein is essentially an exocrine function but its role in the saliva remains obscure. The results suggest that sudden mobilization of kallikrein may occur at times into the saliva and that a separate population of adrenergic axons, under separate central control, may pass to the striated ducts specially for this purpose.