Signaling Networks Regulating Development of the Lower Respiratory Tract

The lungs serve the primary function of air-blood gas exchange in all mammals and in terrestrial vertebrates. Efficient gas exchange requires a large surface area that provides intimate contact between the atmosphere and the circulatory system. To achieve this, the lung contains a branched conducting system (the bronchial tree) and specialized air-blood gas exchange units (the alveoli). The conducting system brings air from the external environment to the alveoli and functions to protect the lung from debris that could obstruct airways, from entry of pathogens, and from excessive loss of fluids. The distal lung enables efficient exchange of gas between the alveoli and the conducting system and between the alveoli and the circulatory system. In this article, we highlight developmental and physiological mechanisms that specify, pattern, and regulate morphogenesis of this complex and essential organ. Recent advances have begun to define molecular mechanisms that control many of the important processes required for lung organogenesis; however, many questions remain. A deeper understanding of these molecular mechanisms will aid in the diagnosis and treatment of congenital lung disease and in the development of strategies to enhance the reparative response of the lung to injury and eventually permit regeneration of functional lung tissue.     

Polish pioneers in research on vertebrate circulatory systems at the Jagiellonian University of Krakow (Poland)

At the end of the XIX century and during the first half of the XX century, Henryk Hoyer and Zygmunt Grodzinski, two eminent Polish researchers, were carring out research on the lymphatic circulatory and blood circulatory systems. Later, these investigations were continued by their students and followers until 1966. Embryos from all groups of vertebrates were used for investigation and on that basis, models of the lymphatic and blood circulatory systems were proposed.     

Squid vascular endothelial growth factor receptor: a shared molecular signature in the convergent evolution of closed circulatory systems

SUMMARY The highly specialized cephalopod cardiovascular system has long been considered a valuable model for understanding the evolution of circulatory systems. Despite the number of studies devoted to this topic, the developmental regulatory mechanisms remain largely unexplored. Here, we focus on the vascular endothelial growth factor receptor (VEGFR). This factor is known to mediate levels of endothelial growth factor that is involved in hematopoiesis and vasculogenesis including multichambered heart development in vertebrates. We found a squid VEGFR ortholog that is expressed in the developing blood vessels, notably in the sheet-like endothelial cells of the systemic and branchial hearts. The highly restricted localization of VEGFR in the vascular endothelial cells and its shared expression pattern in the developing hearts of cephalopods and vertebrates suggest a shared molecular signature of closed circulatory systems that has been independently elaborated during evolution.     

EVOLUTION OF CARDIOVASCULAR BARORECEPTOR CONTROL

During animal evolution the circulatory system has shown a progressive modification in structure, function and short-term control. Short-term circulatory control has evolved from the limitation of a rising blood pressure via a reflex bradycardia to bidirectional control of blood pressure by appropriate reflex changes in heart rate, vascular resistance and impedance. Relevant experimental data ranges from extensive in mammals to nugatory in invertebrates. Baroreceptor research in intervening animal groups is varied, being particularly sparse in birds. This research is reviewed. There are few interspecies comparisons of baroreceptor physiology. Available data is complicated by variation in the techniques employed for assessing baroreceptor function. In non-mammalian research the correlation of heart rate changes to pharmacologically induced changes in blood pressure predominate. In mammalian baroreceptor research methods based upon the ability of discrete baroreceptor sites to effect changes in the peripheral vasculature are more prevalent. All methods are susceptible to modification by other experimental variables, particularly the anaesthetic state of the animal. Available evidence shows a consistent response of a decreasing heart rate to baroreceptor loading throughout the vertebrates, with a progressive increase in the ability of the baroreceptors to change peripheral vascular resistance. These findings are consistent with the known, progressive trend from cholinergic to adrenergic control of the vascular system during evolution. Known baroreceptor sites appear to be located so as to protect the end-organ or-organs primarily at risk from inappropriate blood pressure changes; namely the gill vasculature in the fish, pulmonary circulation in the Amphibia and Reptilia, and the brain and heart in higher animal groups. It is postulated that the carotid sinus baroreceptors have developed in the Mammalia as a second functional baroreceptor site to provide extra protection against hypoperfusion of vital organs, particularly the heart and brain. In humans the dynamic aspects of cardiovascular carotid sinus control, particularly of skeletal muscle flow and integration with cardiopulmonary baroreceptors, may represent a specific response to the adoption of an upright stance. Extremes of environmental stress encountered in contemporary life may exceed the limitation of baroreceptor function in humans, as, for example, during gravitational loading particularly following periods of weightlessness and modification by endurance training.     

Heart position in snakes: response to "phylogeny, ecology, and heart position in snakes"

Here we comment on a recent article (Gartner et al. 2010 ) that addresses previous adaptive interpretations of heart position in the context of gravity effects on blood circulation of snakes. The authors used phylogenetically based statistical methods and concluded that both habitat and phylogeny influence heart position, which they contend is relatively more posterior in arboreal compared to terrestrial species. Their result is based on measurements of heart position relative to snout-vent length, rather than total body length as in previous studies. However, gravity acts on the total length of the arterial-venous vasculature, and caudal segments of continuous blood columns cannot be ignored. Arboreal snakes have relatively long tails; therefore anterior hearts appear to be more "posterior" when the position is described relative to a shorter trunk. There is no physiologically valid explanation for the alleged posterior heart position in arboreal snakes, and multiple lines of published evidence to the contrary are ignored. The authors secondarily evaluated their data set with estimates for total body length based on measurements from other taxa. They found no statistical difference between heart position in arboreal versus terrestrial species, yet their article implied otherwise. Gartner et al. ( 2010 ) contrasted "aquatic" and terrestrial species throughout their paper, and they claimed there is no correlation between heart position and habitat among "aquatic and terrestrial species." But they did not include any aquatic species in their data set. Therefore, the article confuses rather than promotes understanding of cardiovascular adaptation to gravity.     

THE CIRCULATORY SYSTEM OF THE ALDER FLY SIALIS LUTARIA

This is a comprehensive account of the circulatory system of all stages of Sialis lutaria L. The circulatory organs and pathways are described. In the larva an organ for circulating blood within the terminal segment is described. In the adult, blood vessels are described in the appendages and over the surface of the brain. Associated with these vessels are two types of accessory circulatory organs, pulsatile and valvular. The rates of heart beat, of circulation and pulsation of the scutellar organs are recorded.     

Coupled evolution of digestive,respiratory, circulatory,and excretory systems: A model investigation

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems as the single system. The model is realized on the basis of the language STEL-LA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.     

The venous circulation: a piscine perspective.

Vascular capacitance describes the pressure-volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Development of hearing in vertebrates with special reference to anuran acoustic communication

Amphibians, specially anurans, are excellent model systems for studying acoustic communication. After hatching, anurans exist in two forms; these have two distinct mode of sound perception. Aquatic larvae are perceptive to waterborne sound stimuli; then, following metamorphosis, as terrestrial adults, perceptive to airborne sound stimuli. Added to this, the metamorphosing tadpole presents an equally interesting study as it could recapitulate the events which occurred during the evolution of hearing in vertebrates at the lime of the transition from aquatic to terrestrial life. Metamorphosis entails the loss of a prominent aquatic sensory system—the lateral line system—and the simultaneous gain of another, the inner ear, along with the coevolution of the tympanic middle ear, a basilar papilla and a periotic labyrinth in the inner ear. Another interesting feature is that anurans are believed to be the first terrestrial vertebrates to use vocalization as a part of their reproductive behaviour. Vocal communication plays an important role in behaviour, ranging from territorial defense to reproduction, and calls are classified according to the particular behaviors that they subserve. Adult male anurans produce a species-specific mating call which is used to attract conspecific females dung their mating season, and this call serves as a mechanism in maintaining reproductive isolation from other sympatric species.     

Land crabs with smooth lungs: Grapsidae,Gecarcinidae, and Sundathelphusidae ultrastructure and vasculature

The highly terrestrial grapsids and gecarcinids and the amphibious sundathelphusids all have large, expanded branchial chambers. The lining of the branchial chambers is smooth and well vascularized, and it functions as a lung. The respiratory membrane and the cuticle lining the lung are extremely thin (200–350 nm). The blood vessels within the lung are formed from connective tissue cells supported by collagen fibres and lined by a basal lamina. The major vessels in the lung are embedded deep in the branchiostegite and lie just beneath the thick outer carapace. These vessels branch towards the respiratory membrane, where they eventually lose their connective tissue coverings to form thin, flattened lacunae directly below the respiratory epithelium. The lacunae (exchange sites) are bordered by specialized connective tissue cells, which either bear microvilli on their apical surface (fimbriated cells) or are very smooth. The respiratory circulation in the lung is very complex, with two portal systems present between the afferent and efferent systems, producing a total of three lacunal exchange beds. Portal systems increase the surface area available for gas exchange. The major distributing vessel in the lung is the branchiostegal vein, which runs along the inner margin of the branchiostegite. The main venous supplies come anteriorly from the infraorbital and ventral sinuses and posteriorly from the procardial sinus. The main collecting vessel is the pulmonary vein, which arises anteriorly and which runs around the ventral perimeter of the branchiostegite before emptying into the pericardial sinus. © 1993 Wiley-Liss, Inc.     

The venous circulation: a piscine perspective

Vascular capacitance describes the pressure–volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

The effect of environmental factors on circulation and respiration in teleost fish

Summary Anesthesia, handling and activity can produce large variations in some of the parameters of circulation and breathing movements in fish. Handling and MS222 anesthesis cause a large increase in heart rate in the tench, but have the reverse effect on the trout. Hypoxia causes a decreased heart rate and changes in dorsal aortic blood pressure. Serial sampling of the blood appears to have little effect on the parameters of circulation if the blood is replaced with saline. Removal of blood without replacement causes a decrease in blood pressure and a slowing of the heart. It is suggested that much of the variability observed in the measurement of circulatory parameters in fish can be accounted for by the experimental procedure, rather than demonstrating large inter-specific variations in teleost fish.     

Life history of amphibians and gravity.

Anurans hold a unique position in vertebrate phylogeny, as they made the major transition from water to land. Through evolution they have acquired fundamental mechanisms to adapt to terrestrial gravity. Such mechanisms are now shared among other terrestrial vertebrates derived from ancestral amphibians. Space research, using amphibians as a model animal, is significant based on the following aspects: (1) Anuran amphibians show drastic changes in their living niche during their metamorphosis. Environments for tadpoles and for terrestrial life of frogs are quite different in terms of gravity and its associated factors. (2) Certain tadpoles, such as Rhacophorus viridis amamiensis, have a transparent abdominal wall. Thus visceral organs and their motion can be observed in these animals in non-invasive manner through their transparent abdominal skin. This feature enables biologists to evaluate the physiological state of these amphibians and study the autonomic control of visceral organs. It is also feasible for space biologists to examine how such autonomic regulation could be altered by microgravity and exposure to the space environment.     

Coupled evolution of digestive, respiratory, circulatory, and excretory systems: a model investigation

A model is developed of evolution of an organism with digestive, respiratory, circulatory, and excretory systems at the single system. The model is realized on the basis of the language STELLA 8.0. A balance is found between perfection of each individual physiological system and necessary energy expenditures for survival of the organism as a whole. The model is based on a coupled development of several visceral systems. There is analyzed effect of a change of consumption of substances with food and of oxygen amount on their oxidation, a branching of blood flow to organs, specifically to kidneys, to excrete final products of metabolism from blood. The energy expenditures for circulation are believed to be proportional to blood flow in a given organ. An increase of efficiency of renal excretion from blood of final metabolic products and toxic substances has a favorable effect on inner medium and activity of each cell of an individual, but increases of the organism energy expenditures. Interrelation of these factors under conditions of adaptation to changing environmental conditions determines peculiarities of evolution of each physiological system in an individual.     

The lymphatic vasculature in disease

Blood vessels form a closed circulatory system, whereas lymphatic vessels form a one-way conduit for tissue fluid and leukocytes. In most vertebrates, the main function of lymphatic vessels is to collect excess protein-rich fluid that has extravasated from blood vessels and transport it back into the blood circulation. Lymphatic vessels have an important immune surveillance function, as they import various antigens and activated antigen-presenting cells into the lymph nodes and export immune effector cells and humoral response factors into the blood circulation. Defects in lymphatic function can lead to lymph accumulation in tissues, dampened immune responses, connective tissue and fat accumulation, and tissue swelling known as lymphedema. This review highlights the most recent developments in lymphatic biology and how the lymphatic system contributes to the pathogenesis of various diseases involving immune and inflammatory responses and its role in disseminating tumor cells.     

The olfactory receptor gene repertoires in secondary-adapted marine vertebrates: evidence for reduction of the functional proportions in cetaceans

An olfactory receptor (OR) multigene family is responsible for the well-developed sense of smell possessed by terrestrial tetrapods. Mammalian OR genes had diverged greatly in the terrestrial environment after the fish-tetrapod split, indicating their importance to land habitation. In this study, we analysed OR genes of marine tetrapods (minke whale Balaenoptera acutorostrata, dwarf sperm whale Kogia sima, Dall's porpoise Phocoenoides dalli, Steller's sea lion Eumetopias jubatus and loggerhead sea turtle Caretta caretta) and revealed that the pseudogene proportions of OR gene repertoires in whales were significantly higher than those in their terrestrial relative cattle and also in sea lion and sea turtle. On the other hand, the pseudogene proportion of OR sequences in sea lion was not significantly higher compared with that in their terrestrial relative (dog). It indicates that secondary perfectly adapted marine vertebrates (cetaceans) have lost large amount of their OR genes, whereas secondary-semi-adapted marine vertebrates (sea lions and sea turtles) still have maintained their OR genes, reflecting the importance of terrestrial environment for these animals.     

Degeneration patterns of the olfactory receptor genes in sea snakes

The sense of smell relies on the diversity of olfactory receptor (OR) repertoires in vertebrates. It has been hypothesized that different types of ORs are required in terrestrial and marine environments. Here we show that viviparous sea snakes, which do not rely on a terrestrial environment, have significantly lost ORs compared with their terrestrial relatives, supporting the hypothesis. On the other hand, oviparous sea snakes, which rely on a terrestrial environment for laying eggs, still maintain their ORs, reflecting the importance of the terrestrial environment for them. Furthermore, we found one Colubroidea snake (including sea snakes and their terrestrial relatives)‐specific OR subfamily which had diverged widely during snake evolution after the blind snake–Colubroidea snake split. Interestingly, no pseudogenes are included in this subfamily in sea snakes, and this subfamily seems to have been expanding rapidly even in an underwater environment. These findings suggest that the Colubroidea‐specific ORs detect nonvolatile odorants.     

The evolution of the terrestrial vertebrates: environmental and physiological considerations

Physiological evidence has long been used to suggest that the gnathostomous vertebrates (those possessing jaws) were primitively fresh water. The same was also the case for the Osteichthyes (bony fish) and the Tetrapoda (Amphibia, Reptilia, Aves, Mammalia). However, the geological evidence favours a marine origin for the vertebrates as a whole, and, for the gnathostomes and the osteichthyans in particular. Some of the earliest amphibian remains may be associated with tidally influenced sediments. Furthermore, during the early part of the Devonian, fresh water chemistry may well have been different from that of today, lessening the divide between marine and non-marine environments. Urea formation via the ornithine cycle, and urea retention in the body fluids, are useful adaptations for terrestrial life. They prevent excessive water loss associated with the elimination of nitrogenous waste. These abilities may have been primitive for the gnathostomes, and were developed in the marine environment to reduce osmotic dehydration. In the aqueous medium, gaseous exchange is effected by the gills. These organs are, on the whole, useless in air. For vertebrates, air-breathing is effected by an inflatable sac, with moist linings, and an internal location. Some form of air-breathing sac was primitive for the osteichthyans, and may have been primitive for the gnathostomes. Again, this adaptation for terrestrial life developed in response to conditions experienced in the marine, aquatic environment. A new model of tetrapod evolution is proposed in the light of the basic marine origin and character of the ancestors of the tetrapods.     

Mathematical analysis of circulatory mixing process

The circulatory mixing process was analyzed as the time course of the dispersion of indicator after its injection into the heart. In simplified models, which had one or two lumped mixing chambers and circulatory pathways connected with them, it was suggested that the extent of dispersion could be evaluated by the variance of indicator distribution in the total circulating blood when the circulation time distributions between the chambers and the concentration curves in the chambers were known. The method of determining the circulation time distributions through the pulmonary, systemic and total circulations was derived and the actual distributions were obtained in dogs by indicator dilution techniques. With the use of these distributions, the time course of the circulatory mixing process was numerically calculated. The results showed that there was considerable difference in velocities of the process between the case of the right heart injection and the left heart injection of the indicator.