Effect of substrate pretreatment on renal organic ion transport in the adult rat

Summary The ability of renal cortical slices to accumulate PAH and NMN was not significantly affected by pretreatment of adult rats with large doses of PAH. Pretreatment of adult rats with THAM significantly increased PAH accumulation but had no effect on NMN. Inulin and PAH clearance and filtration fraction were significantly decreased by PAH pretreatment but unaffected by THAM pretreatment. The effects of pretreatment on transport are probably due to non-specific toxicity.Supported in part by U. S. Public Health Service Grant No. AM10913.Supported in part by a predoctoral fellowship from the Upjohn Company.Acknowledgments. The technical assistance of Mr.Grant Moore and Ms.Peggy Wagner is gratefully acknowledged.     

Enhancement of tubular organic base accumulation in renal cortical slices by repeated administrations ofTris-hydroxymethyl aminomethane,tromethamol (THAM) to rats of different ages

Summary After repeated THAM administrations to rats of different ages, an enhancement of THAM accumulation in renal cortical slices was observed, except in newborns. This effect can be interpreted as a specific substrate stimulation of the organic base transport system.Acknowledgment. The authors thank MissKarin Müller for technical assistance.     

The influence of pH on the sex-related differences in renal organic ion transport.

The stimulating effects of elevated medium pH and androgen on in vitro transport of p-aminohippurate and N-methylnicotinamide (NMN) were additive, although the androgenic effect was pH-dependent only in the case of NMN. The similarity of response of the 2 systems supports the idea of a common passive efflux pathway for organic anions and cations.     

The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia.

I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine.     

Effects of sham-pinealectomy,performed under white and red light,on the melatonin content of rat pineal glands

Summary Sham-pinealectomy, performed under different light conditions in newborn and adult rats, is followed by changes of pineal activity resulting in variations of melatonin content. The pineal glands of rats sham-operated under white light produce significantly less melatonin. In contrast, glands of rats operated on under red light show a melatonin content corresponding to that of intact rats. This result implies that normal white light causes a disturbance in melatonin production by a non-retinal pathway.     

Cataract induced by administration of a single dose of sodium selenite to suckling rats

Summary A single dose of sodium selenite to male suckling rats causes permanent or intermittent cataracts. The resistance to the lethal effect of selenite in suckling rats is significantly higher in comparison with adult animals.     

The effects of brain monoamine depletion on p-chlorophenyl-alanine-induced hypothermia

Summary I.p. administration of p-chlorophenylalanine produced a fall in rectal temperature in rats. The hypothermia was attenuated after pretreatment of the animals with 5,6-dihydroxytryptamine, but was unaffected after pretreatment of the animals with 6-hydroxydopamine.This work was supported by grants from the National Science Council (Republic of China) and J. Aron Charitable Foundation (USA). The authors are grateful to Dr C.Y. Chai, Dr T.H. Yin, Dr H.H. Lu and Mr C.C. Wei for their advice and support.     

Recent observations on the structure and the properties of yeast NMN adenylyltransferase

A homogeneous preparation of yeast NMN adenylyltransferase (EC 2.7.7.1) showed microheterogeneity, which was revealed by FPLC (Fast Protein Liquid Chromatography) ion exchange chromatography. The resolved components have been characterized with respect to electrophoretic behavior and adenine content. The results led to a hypothesis about a possible role of poly(ADP-ribosylation) in modulating the enzyme activity.     

Recent observations on the structure and the properties of yeast NMN adenylyltransferase

Summary A homogeneous preparation of yeast NMN adenylyltransferase (EC 2.7.7.1) showed microheterogeneity, which was revealed by FPLC (Fast Protein Liquid Chromatography) ion exchange chromatography. The resolved components have been characterized with respect to electrophoretic behavior and adenine content. The results led to a hypothesis about a possible role of poly(ADP-ribosylation) in modulating the enzyme activity.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats.

To study the effect of a sudden loss of body weight on the beta-cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Corticotropin releasing factor increases the adrenocortical responsiveness to adrenocorticotropin

Summary In the course of studying the plasma adrenocorticotropic hormone (ACTH) and corticosterone responses to synthetic corticotropin releasing factor (CRF), we noted some disparity in the responses. A higher dose (20 g compared with 5 g per rat i.a.) produced an equal plasma ACTH but greater plasma corticosterone response in adult male rats. Thus, we examined the possibility that CRF increases adrenocortical responsiveness to ACTH. CRF significantly (p<0.0005) increased the plasma corticosterone response to ACTH in rats pretreated with dexamethasone. Thus, synthetic CRF increases corticosterone secretion in rats not only by stimulating ACTH secretion, but also by increasing the adrenocortical responsiveness to ACTH.Acknowledgments. This research was supported by grant MT-5183 from the Medical Research Council of Canada and by the Department of Medicine, University of Kentucky.     

Critical effects of epigenetic regulation in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterized by persistent pulmonary vasoconstriction and pulmonary vascular remodeling. The pathogenic mechanisms of PAH remain to be fully clarified and measures of effective prevention are lacking. Recent studies; however, have indicated that epigenetic processes may exert pivotal influences on PAH pathogenesis. In this review, we summarize the latest research findings regarding epigenetic regulation in PAH, focusing on the roles of non-coding RNAs, histone modifications, ATP-dependent chromatin remodeling and DNA methylation, and discuss the potential of epigenetic-based therapies for PAH.     

Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ethanol-loaded rats

A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.     

Absorption of iron from gut into blood: Sex- and time-related studies in rats

Summary As judged from 2-h blood level curves, adult female rats absorbed more Fe^II per cm² of gross duodenal mucosa than adult male rats. By contrast, the 2-h blood level curves per cm² of mucosa of proximal jejunum did not differ significantly in male and female rats although in both sexes, iron was absorbed more efficiently from the duodenum. This research was supported by grant RO1 AM 12381 from the National Institute of arthritis, Diabetes and Digestive and Kidney Diseases, National Institutes of Health.     

Lowering of liver acetaldehyde but not ethanol concentrations by pretreatment with taurine in ehtanol-loaded rats

Summary A rise in blood and liver acetaldehyde concentrations following ethanol loading (1.5 g/kg b.wt) was significantly reduced when rats were pretreated orally with taurine (0.5 g/kg), a potent in vitro activator of yeast aldehyde dehydrogenase. This taurine pretreatment produced a 4-fold increase in liver taurine content.     

Beta-adrenergic receptors in rat myocardium: direct detection by a new fluorescent beta-blocker.

A new fluorescent beta-blocker, 9-amino-acridin propranolol (9-AAP), was administered i.v. to rats. Multiple fluorescent 9-AAP binding sites were observed on cardiac muscle cells in frozen sections. Intensity and density of cardiac 9-AAP fluorescence were markedly reduced following pretreatment with (+/-)- and (-)-propranolol but not with (+)-propranolol. Our findings suggest that 9-AAP may label beta-adrenergic receptor sites in rat myocardium.     

Effect of a restricted diet on the in vitro glucose-induced insulin release of aging rats

To study the effect of a sudden loss of body weight on the -cell function of aging rats, basal and glucose-induced insulin secretion was measured in pancreatic islets obtained from young (2-month-old), adult (12-month-old) and aging (24-month-old) rats, either fed ad libitum or fed a restricted diet (50% caloric restriction). Basal insulin secretion was similar in islets of young, adult and older rats. Glucose stimulated insulin release was significantly reduced in aging rats as compared to young animals. Animals fed a restricted diet showed a prolonged and higher secretory rate during first phase release when compared to animals fed ad libitum.     

Zur Frage der entzündungshemmenden Wirkung des Phenylbutazon bei hypothyreotischen Ratten

Summary Following pretreatment of rats by 4-methyl-2-thiouracil the anti-inflammatory action of phenylbutazone on formalin edema is strongly diminuished.     

BMP type II receptor as a therapeutic target in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. The most common cause of PAH is inactivating mutations in the gene encoding a bone morphogenetic protein type II receptor (BMPRII). Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease. Emerging data suggest that restoration of BMPRII signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. Here we will focus on recent advances in rescuing BMPRII expression, function or signaling to prevent and reverse pulmonary vascular remodeling in PAH and its feasibility for clinical translation. Furthermore, we summarize the role of described miRNAs that directly target the BMPR2 gene in blood vessels. We discuss the therapeutic potential and the limitations of promising new approaches to restore BMPRII signaling in PAH patients. Different mutations in BMPR2 and environmental/genetic factors make PAH a heterogeneous disease and it is thus likely that the best approach will be patient-tailored therapies.     

Antihypertensive and cardiac effects of two novel beta-adrenoceptor blocking drugs.

Two new beta-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert.butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert.butylamine-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are like to be at least partially due to stimulation of beta-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.