Showing papers in "Annual Review of Physiology in 1978"

The Renin-Angiotensin System

Abstract: Since the discovery of renin 80 years ago, there have been remarkable advances in our understanding of the renin-angiotensin system. The system as it is known today is summarized in Figure 1. Angiotensin III, the active component of the system, has several important physiological actions. The first of these to be identified was its pressor action, and for many years it was felt that the sole function of the renin-angiotensin system was regula­ tion of blood pressure. A new dimension was added in 1960 with the discovery that angiotensin II stimulates the secretion of aldosterone and is therefore in a position to exert important effects on salt and water balance. Several additional actions of angiotensin II were then discovered. It was found that the peptide can increase the secretion of catecholamines from the adrenal and facilitate adrenergic transmission. It also acts directly on the brain to increase blood pressure via sympathetic and parasympathetic path­ ways, to produce thirst, and to stimulate the secretion of vasopressin and ACTH. Through these actions, the renin-angiotensin system plays an im­ portant role in the regulation of blood pressure and of the volume and composition of the extracellular fluid. Major advances have also been made in our understanding of other aspects of the renin-angiotensin system. It has become clear that the hep­ tapeptide metabolite of angiotensin II, [des-Aspl] angiotensin II ("angio-

Membrane cation transport and the control of proliferation of mammalian cells

Abstract: The cell membrane has a critical role in the control of cell synthesis and metabolism in general, and in the control of cell proliferation in particular; this has been the subject of a number of recent volumes (22, 73, 123). I review here one small aspect of this imposing subject: the relation between cation flux across the membrane and the activation of the cell responses leading to DNA synthesis and cell division. A cascade of morphological, physiological, and biochemical changes follows the initial triggering of cell activation and precedes the DNA syn­ thesis and division; however, not all of these phenomena need be in the train of causally related events which will ultimately lead to mitosis (Figure 1). Some may be outside the mainline sequence (shown in line A); some may be in parallel, but dead-end (line B); others may be in parallel for consider­ able time and then converge on the mainline sequence (line C). Still other events may occur in parallel but be required at all stages in order for the mainline sequence to proceed (line D). It is, of course, vital in studying the role of events like cation fluxes, which are proximal in time to the initial stimulation, to establish their relation to the time-distal events of prolifera­ tion. Otherwise, one risks committing the logical error of post hoc ergo propter hoc, nowhere more frequently encountered in the biological sciences than in that branch which deals with the mechanism of activation of quies­ cent or metastable cells, such as eggs after fertilization or stimulated mam­ malian cells in culture.

Skeletal muscle energetics and metabolism.

Abstract: When muscles contract, chemical energy is converted into mechanical en­ ergy and heat, physical quantities necessary for locomotion, circulation, digestion, respiration, reproduction, and thermal regulation. The task of the muscle energeticist is to learn how much chemical energy is used [and/or heat and work (enthalpy) produced], how chemical energy utilization varies and is regulated, what the mechanism of chemomechanical transduction is, and how substrates used during contraction are restored. To answer these questions, the extent of chemical change (and/or enthalpy production) must be measured. To this end, a variety of techniques have been developed, including measurement of: (a) the muscle's enthalpy production (myother­ mometry); (b) chemical change by quantitative analysis of frozen muscle extracts; (c) chemical change by 31p nuclear magnetic resonance studies of the whole living tissue; (d) oxygen consumption; (e) lactic acid production; (j) the intracellular concentration of NADH; and (g) cellular pH changes. No single technique alone is wholly satisfactory as the general tool for the study of energetics. In some cases a technique lacks the requisite time resolution and/or sensitivity. Other methods require assumptions about the

Respiratory Adaptations in Sleep

Abstract: The current era of research into the physiology of sleep began in 1953 when Aserinsky and Kleitman (2) first described REMl sleep and its association with a characteristic EEG pattern, dreaming, and changes in autonomic nervous system activity including respiration. This important discovery demonstrated conclusively that the traditional view of sleep as a homoge­ neous state was incorrect, and indicated that preexisting observations or theories regarding sleep had to be reexamined or reinterpreted taking the stage of sleep into consideration. Accordingly much of the research in sleep physiology during the past twenty years has been directed towards a defini­ tion of the physiological differences between REM and NREM sleep and towards elucidation of the specific mechanisms and purposes that underlie the different sleep stages. In recent years these same goals have been applied increasingly to the study of respiration during sleep. To the extent that the fundamental purposes and mechanisms of sleep itself remain uncertain, so too are the purposes and mechanisms of the respiratory adaptations to sleep. Nevertheless the changes in respiration that occur in the different stages of sleep have now been studied extensively, at least in purely descrip­ tive terms. In addition, attempts have been made, although fewer in num-

Physiology of the Hippocampus and Related Structures

Abstract: Despite the large number of studies on all aspects of the hippocampus, the function of this structure is still an enigma. In our view multidisciplinary studies of input-output relations integrated with behavioral analytical inves­ tigations hold the greatest promise for a solution to this problem. Therefore, this review is dedicated to the basic physiology of the hippocampus seen as a group of input-output subsystems. The first several sections deal with the functional anatomy and electro­ physiology. This subject receives more intensive treatment in those sections where recent anatomical data obtained with tracer techniques have pro­ vided significant advances. In the second half of the review, hippocampal­ behavior correlates are dealt with. The insight of the authors into these aspects is here given precedence over a detailed review of the extensive literature. The treatment of transmitters and pharmacological aspects is omitted here in view of the recent comprehensive review of Storm-Mathisen ( 194). Several reviews of the physiology of the hippocampus have been published. A classic is that of Brodal (39). The last physiological review is that of Green (86). Since then there have appeared reviews on the phar­ macology of the electrical activity of the hippocampus ( 196); on the physi­ ology of cellular processes (189); and on behavioral correlates of hippocam­ pal function (4, 63, 1l3, 141). The comprehensive book of Isaacson ( 103) gives a survey of the limbic system. A collection of papers on several aspects of hippocampal structure and physiology, its relation to behavior, its devel­ opment and neuroendocrinology has been edited recently by Isaacson & Pribram ( 104). A book covering the Russian literature on the hippocampus has also appeared (76).

Endocrine mechanisms of parturition

Abstract: Intrauterine growth and development follow an orderly sequence of critical phases that influence the several organ systems of the fetus differently at various times. Thus, placental growth and differentiation precede major growth of the fetus. The fetus develops in utero until capable of an indepen­ dent existence outside the uterus. In some mammals, for example the goat, cow, rat, and rabbit, progesterone production by the corpus luteum (CL) of pregnancy continues throughout gestation (51, 61,82-84,193,194,195, 196). In other species, the placenta gradually takes over this role (12, 25, 37, 83, 84, 118, 119, 127, 152, 208). Estrogens are also produced by the ovary and placenta during gestation (4,11,25,31,38,53,84,119,120,136, 156, 169). In the primate species the fetal and maternal adrenals provide precursors for placental estrogen synthesis (87, 164, 169, 175). Other hor­ mones, such as placental lactogen (PL) (chorionic somatomammotrophin) and chorionic gonadotrophin are necessary for normal maternal, placental, and fetal metabolism (51,88,90, 120,201). PL is produced by the syncytio­ trophoblast of the placenta and is a hormone of fetal origin. Thus, both fetal and maternal endocrine factors are of importance in the mechanisms that maintain the pregnant state. The process of parturiton also involves fetal and maternal factors whose role is to remove or supplant these maintenance mechanisms.

Studies of Isolated Renal Tubules In Vitro

Abstract: The conversion of blood into urine is a hallowed function of the kidney. In high forms of life the kidneys contain minute epithelial tubules in a complex array through which the blood filtrate passes in the quiet ritual of urine formation. Over the years a number of experimental approaches have been used to determine how urine is made. From the clearance method, a highly indirect approach, we learned that blood solutes may be filtered, absorbed, and secreted. The so-called "stop-flow" method helped to localize certain transport processes to proximal and distal regions of the renal tubule. The micropuncture technique, adapted for in situ work, served to locate discrete transport processes more clearly. Nevertheless, all of the foregoing methods have been inadequate to study nephron segments buried within the sub­ stance of the kidney or to define specific mechanisms of salt and water transport across the different segments of nephron. Frustrated by the relatively indirect approaches of the day, Dr. Maurice (Moe) Burg of the National Institutes of Health conceived the idea that living tubules should be removed from the kidney and studied in vitro, as one might perfuse an isolated segment of the bowel (12). The initial attempts to perfuse tubules with glass pipets were unsuccessful. The short segments of proximal tubule had been retrieved from a suspension of rabbit kidney cortex prepared by enzymatic digestion with collagenase. Collagenase re-

Localization and Release of Neurophysins

Abstract: The theory of neurosecr etion put forward by Bargmann & Scharrer (6) was based on the concept that the peptide hormones, oxytocin and vasopressin, were synthesiz ed in hypothalamic nuclei, packaged into neurosecretory vesicles, and conveyed by axonal transport to nerve termin als in the neural lobe of the pituitary gland whence they were released into the circulation by appropriate physiologic stimuli. The theory was developed from ana­ tomic studies using the technique of Gomori (38) to demonstrate that the central nervous system combined neural and endocrine functions. Barg­ mann (4, 5) observed that the acid-p ermanganate chrom-alum-haema

Rhapsody in science (PF Scholander).

Abstract: Dear readers, I find it quite shocking to have reached a stage in life when I am supposed to be retrospective. Like a vulgar streaker I shall expose myself in the limelight. I frequently ask myself how has it been possible to live such an exciting and happy life being such an irregular and irresponsible person? My Norwegian mother was an accomplished pianist. I have just noticed in her copy of Speemans' encyclopedia, Goldenes Buch der Musik (1909), that she underlined the following advice to prospective musicians (which in my opinion applies to scientists as well): “Only such a person can I advise to become an artist, who from pure love of art itself, through internal urge and need—unconcerned about spectacular successes—desires to devote his life to it and therein to find his fulfillment and his happiness.”

Relationship of renal sodium and water transport to hydrogen ion secretion.

Abstract: In recent years it has become increasingly clear that the kidney's regulation of volume homeostasis via its control of salt and water reabsorption is inextricably linked with its regulation of hydrogen ion secretion. The pur­ pose of this review is to outline some of the processes that control hydrogen ion secretion both in the proximal and distal nephron and to detail how these functions are related to volume regulation. This report further out­ lines the difficulty sometimes encountered in assessing hydrogen ion secre­ tory capacity. Such difficulties arise because salt and water reabsorption may influence parameters usually thought to reflect hydrogen ion secretory ability only. In other words, the demands of volume regulation, both on the bulk reabsorption of salt and water in the proximal tubule and on the reabsorption of salt in the ascending limb of the loop of Henle with its concomitant influence on water transport in the collecting duct, may alter tests of urinary acidification so that they seem to indicate acidification defects when none may actually exist. ....