Vascular development in chick embryos: a possible role for adenosine

1989 ◽  
Vol 256 (1) ◽  
pp. H240-H246 ◽  
Author(s):  
T. H. Adair ◽  
J. P. Montani ◽  
D. M. Strick ◽  
A. C. Guyton

We studied the possible role of adenosine in the development of the vasculature using 217 chick embryos. Adenosine (2-32 mumol/day), inosine (16 mumol/day), dipyridamole (0.04-0.4 mumol/day), or aminophylline (400 and 800 micrograms/day) were administered twice each day into the air space on days 11-14. Control embryos received Ringer solution. Whole body vascularity was estimated on day 15 as the whole body structural vascular resistance (SVR), i.e., the hydraulic resistance of the maximally dilated vasculature. Adenosine decreased the SVR in a dose-related manner at the lower dosage amounts but caused a maximum decrease in SVR at the higher dosage amounts averaging 30% below the Ringer control values. Equimolar amounts of adenosine and inosine decreased the SVR by the same extent. Dipyridamole, which potentiates the biological effects of endogenous adenosine, also decreased the SVR in a dose-related manner to values averaging approximately 30% below control. When the effects of endogenous adenosine were blocked by aminophylline, the SVR increased in a dose-related manner to approximately 100% above control at the highest dosage amount. These results suggest that adenosine could have a physiological role in growth regulation of the vascular system in the chick embryo.

2012 ◽  
Vol 140 (9-10) ◽  
pp. 595-599 ◽  
Author(s):  
Snezana Palcevska-Kocevska ◽  
Natasa Aluloska ◽  
Marija Krstevska ◽  
Elena Shukarova-Angelovska ◽  
Ljiljana Kojik ◽  
...  

Introduction. It has been shown that some adipocytokines and their mutual relationship can be indicators of fetal and neonatal growth. Physiological role of leptin and adiponectin in fetal and neonatal growth is not well established. Objectives. The aim of this study was to assess the correlation of the anthropometrics parameters and serum concentration of leptin and adiponectin levels in healthy newborns. Methods. A cohort of 110 neonates, born after uncomplicated singleton pregnancies at term, were classified as AGA (n=60), SGA (n=30) and LGA (n=20) according to the Lubchenco curves. Anthropometric parameters of the neonates: birth weight (BW), birth length (BL), body weight/body length ratio (BW/ BL), Body Mass Index (BMI) and Ponderal Index (PI) were recorded after birth. Results. Mean serum leptin and adiponectin levels in both sexes were not significantly different (male: 1.85?0.75; 29.51?22.89 and female: 2.06?0.99; 31.60?23.51 ng/mL). There was a significant difference between leptin levels in AGA and LGA newborns (1.93?0.84 vs. 3.12?1.50 ng/mL) (p<0.05), and in adiponectin levels between AGA and LGA compared to SGA newborns (32.8?23.29 and 43.40?31.24 vs. 12.67?2.43 ng/mL, respectivel; p<0.05; p<0.05). Leptin and adiponectin levels were positively correlated with BW (r=0.63 and r=0.41), BL (r=0.63, r=0.42), BW/BL (r=0.61, r=0.41), BMI (r=0.54, r=0.35), and PI (r=0.47, r=0.29, (p<0.01). Conclusion. Significantly higher adiponectin levels were found in AGA neonates compared to SGA neonates. Leptin and adiponectine levels were positively correlated with birth weight. These findings suggest that these adipocytokines may be involved in fetal growth regulation.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Audrey Sambeat ◽  
Joanna Ratajczak ◽  
Magali Joffraud ◽  
José L. Sanchez-Garcia ◽  
Maria P. Giner ◽  
...  

Abstract Supplementation with the NAD+ precursor nicotinamide riboside (NR) ameliorates and prevents a broad array of metabolic and aging disorders in mice. However, little is known about the physiological role of endogenous NR metabolism. We have previously shown that NR kinase 1 (NRK1) is rate-limiting and essential for NR-induced NAD+ synthesis in hepatic cells. To understand the relevance of hepatic NR metabolism, we generated whole body and liver-specific NRK1 knockout mice. Here, we show that NRK1 deficiency leads to decreased gluconeogenic potential and impaired mitochondrial function. Upon high-fat feeding, NRK1 deficient mice develop glucose intolerance, insulin resistance and hepatosteatosis. Furthermore, they are more susceptible to diet-induced liver DNA damage, due to compromised PARP1 activity. Our results demonstrate that endogenous NR metabolism is critical to sustain hepatic NAD+ levels and hinder diet-induced metabolic damage, highlighting the relevance of NRK1 as a therapeutic target for metabolic disorders.


2002 ◽  
Vol 80 (5) ◽  
pp. 579-596 ◽  
Author(s):  
Richard D Vaughan-Jones ◽  
Kenneth W Spitzer

Bicarbonate is important for pHi control in cardiac cells. It is a major part of the intracellular buffer apparatus, it is a substrate for sarcolemmal acid-equivalent transporters that regulate intracellular pH, and it contributes to the pHo sensitivity of steady-state pHi, a phenomenon that may form part of a whole-body response to acid/base disturbances. Both bicarbonate and H+/OH– transporters participate in the sarcolemmal regulation of pHi, namely Na+–HCO3– cotransport (NBC), Cl––HCO3– exchange (i.e., anion exchange, AE), Na+–H+ exchange (NHE), and Cl––OH– exchange (CHE). These transporters are coupled functionally through changes of pHi, while pHi is linked to [Ca2+]i through secondary changes in [Na+]i mediated by NBC and NHE. Via such coupling, decreases of pHo and pHi can ultimately lead to an elevation of [Ca2+]i, thereby influencing cardiac contractility and electrical rhythm. Bicarbonate is also an essential component of an intracellular carbonic buffer shuttle that diffusively couples cytoplasmic pH to the sarcolemma and minimises the formation of intracellular pH microdomains. The importance of bicarbonate is closely linked to the activity of the enzyme carbonic anhydrase (CA). Without CA activity, intracellular bicarbonate-dependent buffering, membrane bicarbonate transport, and the carbonic shuttle are severely compromised. There is a functional partnership between CA and HCO3– transport. Based on our observations on intracellular acid mobility, we propose that one physiological role for CA is to act as a pH-coupling protein, linking bulk pH to the allosteric H+ control sites on sarcolemmal acid/base transporters.Key words: bicarbonate transporter, pHi, heart, ventricular.


1997 ◽  
Vol 152 (3) ◽  
pp. 339-344 ◽  
Author(s):  
V A Blakesley ◽  
B S Stannard ◽  
T Kalebic ◽  
L J Helman ◽  
D LeRoith

Introduction The insulin-like growth factor-I (IGF-I) receptor is a transmembrane protein tyrosine kinase which mediates the biological effects of IGF-I (LeRoith et al. 1995, Nissley & Lopaczynski 1991) and most of the actions of insulinlike growth factor-II (IGF-II). Binding of IGF-I to the IGF-I receptor results in receptor autophosphorylation, phosphorylation of intracellular substrates and activation of specific signaling processes involved in growth regulation and differentiation (Lowe 1991). The role of the IGF-I receptor in normal mammalian development is exemplified by the work of Efstratiadis and co–workers on mice that carried a null mutation for the IGF-I receptor gene (Baker et al. 1993, Liu et al. 1993c). The growth in utero of these mice is severely inhibited and the mice die immediately after birth. Fibroblasts derived from these mice cannot grow in IGF-I-supplemented serum-free medium whereas mouse fibroblasts with functional IGF–I receptors are capable of growth (Sell et al. 1994), suggesting


2020 ◽  
Vol 10 (9) ◽  
pp. 583
Author(s):  
Patrick S. Hosford ◽  
Natalia Ninkina ◽  
Vladimir L. Buchman ◽  
Jeffrey C. Smith ◽  
Nephtali Marina ◽  
...  

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ−/−) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ−/− male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.


1988 ◽  
Vol 254 (6) ◽  
pp. H1194-H1199
Author(s):  
T. H. Adair ◽  
J. P. Montani ◽  
A. C. Guyton

We explored whether the blood vascular system of the chick embryo adapts its structure to meet the maximum or average oxygen needs of the tissue cells. Chick embryos were grown in continuous 12% oxygen, continuous 16% oxygen, and intermittent 12% oxygen in which the embryos were exposed to 12% oxygen for 4 h each day. Control groups were grown in room air. Measurements of structural vascular resistance (SVR), i.e., the resistance of the maximally dilated vasculature, were used to estimate the whole body vascularity of the 14- or 15-day-old embryos. Continuous exposure to 12% oxygen decreased SVR by 63.1 +/- 1.2 (SE) %, and intermittent exposure to 12% oxygen decreased SVR by 55.6 +/- 0.5% when compared with a 15-day-old normoxic control group. Based on studies with continuous exposure to different levels of low oxygen, it was predicted that exposure to 19.5% oxygen, the average concentration for the intermittent hypoxia group, would decrease SVR by 15.0 +/- 0.3%. These results indicate that intermittent hypoxia at 12% oxygen was approximately 90% as effective as continuous hypoxia at the same level in decreasing SVR and about four times more effective than 19.5% continuous oxygen. Therefore, the results support the hypothesis that the blood vascular system adapts its structure to meet almost entirely the maximum oxygen needs of the tissue cells.


2020 ◽  
Vol 79 (1) ◽  
pp. 76-87
Author(s):  
Leonardo M de Souza Mesquita ◽  
Laís V Mennitti ◽  
Veridiana V de Rosso ◽  
Luciana P Pisani

Abstract Vitamin A (VA) and its pro-vitamin carotenoids are naturally occurring lipophilic compounds involved in several cellular processes and metabolic pathways. Despite their broad spectrum of activities in the general population, dietary deficiencies of these compounds can potentially affect pregnancy outcomes. Since maternal nutritional status and diet composition during pregnancy and lactation can have long-lasting effects in offspring until adulthood, this study presents an overview of VA and the role of pro-VA carotenoids during pregnancy and lactation – the nutrition, metabolism, and biological effects in the offspring. The review aimed to discuss the pro-VA carotenoids and VA-associated pathways and summarize the results with reference to gestational disorders, and VA and pro-VA carotenoids as preventive agents. Also, considering that obesity, overweight, and metabolic diseases are major public health concerns worldwide, fetal and neonatal development is discussed, highlighting the physiological role of these molecules in obesity prevention. This review comprehensively summarizes the current data and shows the potential impact of these compounds on nutritional status in pregnancy and lactation.


1987 ◽  
Vol 252 (6) ◽  
pp. H1228-H1234 ◽  
Author(s):  
T. H. Adair ◽  
A. C. Guyton ◽  
J. P. Montani ◽  
H. L. Lindsay ◽  
K. A. Stanek

We studied the role of hypoxia in the development of the blood vascular system using functional measurements of whole body and hindlimb structural vascular resistance in the chick embryo. The method is based on a newly developed whole body perfusion technique in which the maximally dilated blood vasculature of 14- to 15-day chick embryos is perfused through the extraembryonic blood vessels. Embryos were grown in 12% oxygen (Po2 65 mmHg, n = 18) or 16% oxygen (Po2 96 mmHg, n = 19) for the last 7 days of incubation and were compared with weight-matched (n = 17) and age-matched (n = 18) normoxic control groups (Po2 134 mmHg). Pressure-flow curves were generated for all embryos by increasing and decreasing the aortic pressure along 1-mmHg steps over a pressure range of 0-6 mmHg. Venous pressure was held at 0 mmHg by allowing the perfusate to flow freely from severed extraembryonic veins. The hydraulic resistance of the maximally dilated vascular bed, called the "structural vascular resistance," was decreased in a dose-related manner in the hypoxic groups to greater than 50% of control in the whole body and hindlimbs of the 12% oxygen group. The vessels of the 12% oxygen group were able to carry two and three times as much flow to the whole body and hindlimb tissues, respectively, as compared with the weight-matched normoxic control group. Therefore, the results support the hypothesis that prolonged exposure to hypoxia causes the blood vascular system to adapt its structure to allow greater amounts of blood to flow to the tissues at any given perfusion pressure gradient.


1985 ◽  
Vol 106 (3) ◽  
pp. 377-386 ◽  
Author(s):  
M. J. Waters ◽  
V. H. Oddy ◽  
C. E. McCloghry ◽  
P. D. Gluckman ◽  
R. Duplock ◽  
...  

ABSTRACT The physiological role of placental lactogen (PL; chorionic somatomammotrophin) in the ewe has been investigated by infusion of ewes (n = 3) on day 131 of pregnancy with sufficient ovine PL (oPL) antibody to neutralize circulating oPL for at least 12 h. Effectiveness of the antibody neutralization was defined both in vitro and in vivo according to rigorous criteria. Control ewes (n = 3) were infused simultaneously with an equivalent amount of pooled goat gamma globulin. Since both sets of ewes had previously been catheterized with jugular, utero-ovarian and femoral vein catheters and a femoral arterial catheter, it was possible to measure whole body glucose kinetics as well as muscle and uterine glucose, free fatty acid (FFA) and 3-hydroxybutyrate extraction. In addition, plasma levels of insulin, GH, prolactin, insulin-like growth factor-I (IGF-I), IGF-II, progesterone and cholesterol were determined in femoral arterial samples. Neutralization of maternal oPL did not significantly affect whole body glucose metabolism, uterine and muscle glucose extraction, or 3-hydroxybutyrate extraction by muscle. A trend towards lower plasma FFA levels was observed after prolonged infusion, but was not statistically significant. However, plasma insulin levels rose significantly during antibody infusion after an early fall. These observations are rationalized in terms of the known requirements of ruminant metabolism during pregnancy, and contrasted with the accepted model for the role of human PL in the metabolic adjustments of pregnancy. No change in plasma IGF-I, IGF-II or GH was observed, providing no support for the concept that oPL is responsible for maternal somatomedin generation during pregnancy. Similarly, plasma prolactin did not differ between antibody-treated and control groups. Finally, antibody neutralization had no influence on either plasma progesterone or cholesterol, mitigating against a role for oPL in progesterone production during late pregnancy in the ewe. J. Endocr. (1985) 106, 377–386


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