bluuebunny/crossref_metadata_2025_split huggingface dataset:
HORMONES AS LONG‐TERM ERROR SIGNALS FOR THE SYMPATHETIC NERVOUS SYSTEM: IMPORTANCE OF A NEW PERSPECTIVE
Authors: Osborn John W. 
Published: June 2007

SUMMARY1. A hormonal‐sympathetic reflex model for long‐term control of arterial pressure is presented. It is hypothesized that the hormonal‐sympathetic reflex regulates arterial pressure during chronic dietary salt loading by decreasing sympathetic tone. This sympathetic response is mediated by an increase in plasma vasopressin (AVP) and a decrease in plasma angiotensin (AngII).2. Three new models of neurogenic salt‐dependent hypertension are presented. All models are theoretically based on an impaired hormonal‐sympathetic reflex.3. In the first model, sympathetic responsiveness is ‘clamped’ by long‐term α‐adrenergic blockade with prazosin. Prazosin treated rats exhibit marked salt‐dependent hypertension despite normal suppression of the renin‐angiotensin system.4. In the second model, the ability of the central nervous system to respond to salt‐induced changes in AVP and AngII concentrations was prevented by long‐term administration of antagonists selective for the AVP‐V1 and AT1. This ‘clamp’ of the afferent hormonal signal resulted in salt‐dependent hypertension identical in magnitude to that observed in prazosin treated rats.5. In the third model, the long‐term arterial pressure responses to increasing dietary salt were examined in sino‐aortic denervated (SAD) rats. SAD rats exhibited salt‐dependent hypertension, of lesser magnitude than that observed with ‘clamped’ afferent and efferent pathways of the hormonal‐sympathetic reflex.6. A primary role for hormonal ‘error signals’ is presented and the impact this perspective has on past and future investigations of central mechanisms of long‐term arterial pressure regulation is discussed.
CIRCULATING Na+/K+‐ATPase INHIBITORS: EFFECTS OF NEUROPEPTIDES, VOLUME EXPANSION AND SALT LOADING IN CONSCIOUS RATS
Authors: Schmitt Bernhard M. , Unger Thomas , Rettig Rainer 
Published: June 2007

SUMMARY1. In mammalian plasma, many different inhibitors of Na+/K+‐ATPase are present, but it is not clear whether their net effect on Na+/K+‐ATPase activity changes during the regulation of electrolyte and fluid balance. We studied Na+/K+‐ATPase inhibition by plasma extracts in conscious rats during short‐and long‐term body fluid regulation.2. Male, adult, conscious, freely moving Wistar rats were subjected to one of the following protocols: (i) intracerebroventricular (i.c.v.) injections of angiotensin II (Angll; 1, 10 and 100 ng), the Angll receptor antagonist losartan (1μg), atrial natriuretic peptide (ANP‐III; 1μg) or isotonic saline (IS); (ii) intra‐arterial (i.a.) injections of IS (6 or 10 mL), hypertonic saline (HS; 1.2% NaCl, 5 mL) or hypertonic plasma expander (HPS; 3.5% hetastarch in HS, 5mL); or (iii) a low salt‐high salt‐low salt diet sequence (0.18/1.8/0.18% NaCl chow for S days each with controls receiving 0.18% NaCl on all days). Bodyweight, the intake of food and water, urine volume and Na+ concentration and weight of faeces were determined daily. Plasma samples were withdrawn repeatedly throughout the respective protocols, extracted on C18‐reversed phase columns and assayed for their effect on the activity of different Na+/K+‐ATPase preparations.3. The inhibition of rat brain Na+/K+‐ATPase by plasma extracts was not significantly changed by i.c.v. injection of Angll, losartan, ANP‐III and IS within the observation period (30 min from respective stimuli). Similarly, no significant changes occurred after acute volume expansion by i.a. injection of IS or HS within 120 min; upon HPS, however, Na+/K+‐ATPase inhibition was decreased by approximately 20% (P<0.05), probably due to passive dilution. During the high‐salt diet, fluid retention was effectively counteracted by an adaptive increase of urinary sodium excretion. Throughout the protocol, inhibition of pig brain Na+/K+‐ATPase by plasma extracts did not differ significantly between groups.4. It is concluded from these results that the short‐ or long‐term control of body fluids in conscious rats is not associated with systematic changes in Na+/K+‐ATPase inhibition by plasma factors.
EFFECT OF NG‐M0N0METHYL‐L‐ARGININE ON THE MICROCIRCULATION OF RAT SKIN
Authors: Kakizoe Eiichi , Kobayashi Yuta , Okunishi Hideki , Shimoura Keiko , Jidoi Joji , Hattori Keisuke 
Published: June 2007

SUMMARY1. The effects of NG‐monomethyl‐L‐arginine (L‐NMMA), a nitric oxide (NO) synthase inhibitor, on the microcirculation of rat dorsal skin were studied to examine the role of NO in the regulation of regional haemodynamics.2. The blood volume in the skin microcirculation, which was continuously measured by reflectance spectrophotometry, was significantly decreased in response to L‐NMMA (10 mg/kg bodyweight, i.v.), suggesting vasoconstriction, and the response continued for more than 20 min. In contrast, the increase in systemic blood pressure (BP) disappeared soon after administration of L‐NMMA.3. These results show that L‐NMMA elicits long‐lasting responses in the skin microcirculation, whereas the systemic BP rapidly recovers, suggesting a large contribution of the NO system to the regulation of rat skin microcirculation.
INCREASED KALLIKREIN ACTIVITY IN THE RABBIT RENAL VASCULATURE DURING LOW SODIUM INTAKE
Authors: Kuo Jay J. , Zimmerman Ben G. 
Published: June 2007

SUMMARY1. Vascular tissue has been shown to possess a kallikrein ‐kinin system that may participate in the kinin‐mediated increase in renal sodium excretion. As sodium deprivation has been demonstrated to increase kallikrein content in the kidney and urine we hypothesized that during low sodium intake, kallikrein should increase in the renal vasculature.2. Kininogenase activity, reflecting kallikrein enzymatic content, was measured in a homogenate of a microdissected intrarenal arterial network (IAN) from the rabbit kidney. Kininogenase activity was determined in rabbits on a normal sodium (n= 14) or sodium‐restricted (n—9) diet.3. Total kininogenase activity in rabbits on a normal sodium diet was 15.0 ± 2.7 pg kinin/mg per 30 min, while it was much higher in rabbits on a sodium‐restricted diet (90.7 ± 16.5 pg kinin/mg per 30 min). Specific tissue kallikrein activity was measured by comparing the difference in kininogenase activity in homogenates treated with soybean‐trypsin inhibitor (SBTI) compared with homogenates treated with SBTI and aprotinin. This difference was much larger in the sodium‐restricted rabbits than in rabbits on a normal sodium diet (29.5 ±3.8 vs 5.1 ± 1.7 pg kinin/mg per 30 min, respectively).4. We conclude that the rabbit IAN produces kallikrein, which is markedly increased in response to sodium restriction. Increased kinins during sodium restriction may modulate the pressor and anti‐natriuretic systems activated during negative sodium balance.
LACK OF EFFECT OF AGE ON THE CARDIOVASCULAR RESPONSE TO NEUROPEPTIDE Y INJECTION IN THE RAT NUCLEUS TRACTUS SOLITARIUS
Authors: Morris Margaret J. , Pavia Jillian M. 
Published: June 2007

SUMMARY1. Neuropeptide Y (NPY) is colocalized with catecholamines in central regions involved in blood pressure regulation and exerts depressor responses in the nucleus tractus solitarius (NTS). Ageing is accompanied by a decline in baroreflex function and a reduction in NPY concentrations in some brain areas. The present study investigated whether the cardiovascular response to NPY microinjection into the NTS and medullary NPY concentrations were conserved in aged rats.2. Neuropeptide Y (6 pmol in 100 nL) unilaterally injected into the NTS of anaesthetized 3‐ or 17‐month‐old male Sprague‐Dawley rats produced a prompt 9–10% fall in mean arterial pressure (MAP), which tended to last longer in aged rats. Decreases in heart rate (HR) observed following NPY administration into the NTS were modest but more prolonged than the depressor responses, ANOVA with repeated measures demonstrated no significant effect of age on the MAP or HR response to NPY injection into the NTS. Neuropeptide Y concentrations in the dorsomedial and ventrolateral medulla were not different between the two age groups.3. Thus, the depressor and bradycardic responses to exogenous NPY administration in the NTS were maintained with age, in keeping with the observation of similar medullary NPY concentrations in adult and aged rats.
BRIEF REVIEW BIOLOGY OF GUT CHOLECYSTOKININ AND GASTRIN RECEPTORS
Authors: Shulkes Arthur , Baldwin Graham S. 
Published: June 2007

SUMMARY1. The stomach hormone gastrin and the intestinal hormone cholecystokinin (CCK) share a common C‐terminal pentapep‐tide sequence but have different biological roles. Gastrin is the major stimulant of gastric acid secretion and has a growth stimulatory effect on the secretory part of the stomach. The physiological roles of CCK are the stimulation of pancreatic secretion and the contraction of the gall‐bladder.2. Several classes of receptors have been defined for peptides of the gastrin/CCK family. The CCKA receptor on pancreatic acini has a greater affinity for sulfated CCK than for gastrin, while the gastrin/CCKB receptor in gastric mucosa and brain has similar affinities for both gastrin and CCK. Potent and selective antagonists have been developed for both receptor classes.3. The structures of the CCKA and gastrin/CCKB receptors have been deduced from the nucleotide sequences of cloned cDNA. The receptors, which both belong to the family with seven transmembrane segments, control secretion via similar signalling mechanisms. Occupation of either receptor leads to activation of phospholipase C, with resultant increases in intracellular levels of inositol triphosphate and Ca2+. Mitogenic signalling pathways are also being defined.4. Recent studies have questioned the previous assumption that gastrin precursors are inactive. Glycine‐extended gastrin has been shown to stimulate mitogenesis in some cell lines and may also have an autocrine role in the growth of colonic cancers. The receptors involved, which are clearly distinct in binding properties from the CCKA and gastrin/CCKB receptors, have not yet been cloned. Specific antagonists for the novel receptors will be required to define their function in further detail.
ANGIOTENSIN II‐GENERATING SYSTEM IN DOG AND MONKEY OCULAR TISSUES
Authors: Shiota Naotaka , Saegusa Yumiko , Nishimura Kazuo , Miyazaki Mizuo 
Published: June 2007

SUMMARY1. Angiotensin II (Angll) is generated locally in several tissues, including ocular tissues. Recently, it has been suggested that in addition to angiotensin‐converting enzyme (ACE), an alternative Angll‐generating enzyme, chymase, is present in the cardiovascular tissues of humans, monkeys and dogs and may be involved in the local production of Angll. The purpose of the present study was to determine whether chymase contributes to Angll generation in dog and monkey ocular tissues and to clarify the intraocular Angll‐generating system.2. Chymase‐like and ACE activities were measured in dog and monkey ocular tissues, carotid artery, heart and lung. Their mRNA levels were quantified using the competitive reverse transcriptase‐polymerase chain reaction (RT‐PCR) method.3. Chymase‐like activity was detected in the anterior uveal tract, choroid and sclera in dog eyes, but not in the cornea, lens or fluid phase (vitreous body and aqueous humor). In monkey eyes, chymase‐like activity was detected in the anterior uveal tract and it was higher here than in the heart. Angiotensin‐converting enzyme activity was detected in the anterior uveal tract, choroid, retina, sclera and fluid phase in both dog and monkey eyes. Chymase and ACE mRNA were detected in tissues showing enzymatic activity.4. These findings show for the first time that chymase, in addition to ACE, is expressed locally in dog and monkey ocular tissues and may be involved in local Angll generation in the eye.
IS ATHEROSCLEROSIS EXCLUSIVELY A POSTPRANDIAL PHENOMENON?
Authors: Mamo John CL , Yu Kenneth CW , Elsegood Caryn L. , Smith Darrin , Vine Donna , Gennat Hanni C. , Voevodin Melanie , Proctor Spencer D. 
Published: June 2007

SUMMARY1. Atherosclerosis begins with the deposition of cholesterol in arterial tissue that is thought to be derived from circulating lipoproteins. There is considerable evidence implicating low density lipoprotein (LDL) as a primary source of plaque cholesterol and, consequently, there are many articles that deal with various aspects of LDL metabolism.2. Postprandial lipoproteins (i.e. chylomicrons transporting dietary fats) are also considered pro‐atherogenic; however, it is less clear whether their involvement in arterial cholesterol deposition is direct or follows modulation of LDL metabolism.3. In order to provoke discussion, this article is presented in a manner that suggests atherosclerosis to be exclusively a postprandial phenomenon; that is, we have raised the possibility that LDL is non‐atherogenic.
ROLE OF NITRIC OXIDE IN TUBULOGLOMERULAR FEEDBACK: EFFECTS OF DIETARY SALT
Authors: Welch William J. , Wilcox Christopher S. 
Published: June 2007

SUMMARY1. The tubuloglomerular feedback (TGF) response operates primarily by vasoconstriction of the afferent arteriole and a fall in glomerular capillary pressure (PGC) and single‐nephron glomerular nitration rate (SNGFR) during increased NaCl reabsorption in the macula densa (MD). Numerous studies have suggested that nitric oxide (NO) is synthesized by the MD and acts to suppress TGF. As a high‐salt (HS) diet has been found to blunt TGF, we tested the effects of salt intake on NO‐dependent changes in TGF.2. In the first series of experiments, values of SNGFR were contrasted from samples of tubular fluid taken from the proximal tubule (PT; MD delivery interrupted) and the distal tubule (DT; MD delivery intact). Compared with HS rats, the difference between PT and DT values of SNGFR was increased in low‐salt (LS) diet rats (4.3 ± 0.4 vs 10.3 ± 1.2 nL/min, respectively; P < 0.001). Intravenous infusion of iVG‐monomethyl‐L‐arginine (L‐NMMA), in pressor doses increased the difference between PT and DT values of SNGFR of HS rats (4.3 ± 0.4 vs 9.5 ± 1.2 nL/min before and during L‐NMMA, respectively; P < 0.001) without significantly affecting values in LS rats (10.3 ± 1.2 vs 12.3 ± 1.4 nL/min before and during L‐NMMA, respectively; NS).3. A second series of experiments assessed TGF responses directly. Changes in stop‐flow pressure (PSF; an index of PGC) were measured in response to graded perfusion of the loop of Henle (LH) with artificial tubular fluid. Loop perfusion with 10‐3 mol/1. L‐NMMA did not affect the PSF responses of LS rats but did reduce (P < 0.01) the PSF of HS rats during perfusion at 20 nL/min (‐1.5±0.4mmHg; P<0.01), 30nL/min (‐1.8 ± O.5 mmHg; P < 0.01) and 40 nL/min (‐2.2 ± 0.5 mmHg; P < 0.001).4. We conclude that the TGF response is increased by suppression of NOS activity during HS but not LS intake.
ROLE OF NITRIC OXIDE IN THE CONTROL OF THE RENAL MEDULLARY CIRCULATION
Authors: Mattson David L. , Lu Shanhong , Jr Allen W Cowley 
Published: June 2007

SUMMARY1. Nitric oxide (NO) has been implicated as an important controller in the short‐ and long‐term regulation of arterial pressure. Studies performed in our laboratory have demonstrated that chronic intravenous administration of the NO synthase inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) selectively decreases renal medullary blood flow, causes sodium and water retention and leads to hypertension.2. To determine the importance of the renal medullary effects in this model of hypertension, further studies were conducted to examine the influence of selective stimulation or inhibition of renal medullary NO on whole kidney function and cardiovascular homeostasis. With the use of a unique catheter to directly infuse into the renal medullary interstitial space, stimulation (bradykinin or acetylcholine) or inhibition (L‐NAME) of renal medullary NO selectively increased or decreased renal medullary blood flow.3. The changes in medullary flow in these experiments were associated with parallel changes in sodium and water excretion independent of alterations in renal cortical blood flow or glomerular filtration rate.4. Studies were then undertaken to examine the long‐term effects of selective NO inhibition in the renal medulla on cardiovascular homeostasis. Chronic infusion of L‐NAME directly into the renal medullary interstitial space of uninephrectomized Sprague‐Dawley rats led to a selective decrease in renal medullary blood flow that was sustained throughout the 5 day L‐NAME infusion period. The decrease in medullary blood flow was associated with retention of sodium and the development of hypertension and the effects were reversible.5. The data reviewed indicate that NO in the renal medulla has a powerful influence on fluid and electrolyte homeostasis and the control of blood pressure.
NITRIC OXIDE IN THE MEDIATION OF PRESSURE NATRIURESIS
Authors: Majid DSA , Navar LG 
Published: June 2007

SUMMARY1. Recent studies have indicated that nitric oxide (NO) production in the kidney contributes to the regulation of renal haemodynamics and excretory function. Inhibition of nitric oxide synthase (NOS) reduces renal blood flow by approximately 25% and markedly reduces sodium excretion without reductions in filtered load. In particular, inhibition of NO synthesis markedly suppresses the slope of the arterial pressure‐mediated response in sodium excretion.2. Further studies have shown that constant intrarenal infusion of a NO donor in dogs treated with a NOS inhibitor produced diuretic and natriuretic responses but failed to restore the slope of the pressure‐induced natriuretic response. These data indicate that an alteration in intrarenal NO activity, rather than the simple presence of NO during changes in arterial pressure is required for full expression of pressure natriuretic responses.3. In support of the hypothesis that NO is involved in the mediation of pressure natriuresis, we also recently demonstrated a direct relationship between changes in arterial pressure and urinary excretion rate of sodium as well as nitrate and nitrite (a marker for endogenous NO activity) in the presence of efficient autoregulation of cortical and medullary blood flow.4. The direct inhibitory actions of NO on tubular sodium reabsorption have also been observed in cultured tubular cells as well as isolated, perfused cortical collecting duct segments.5. Thus, the collective data suggest that acute changes in arterial pressure induce changes in intrarenal NO production, which may directly alter tubular reabsorptive function to manifest the phenomenon of pressure natriuresis.
NITRIC OXIDE, THE KIDNEY AND HYPERTENSION
Authors: Schnackenberg C. , Patel AR , Kirchner KA , Granger JP 
Published: June 2007

SUMMARY1. According to the renal body fluid feedback mechanism for long‐term control, persistent hypertension can only occur as a result of a reduction in renal sodium excretory function or a hypertensive shift in the pressure natriuresis relationship. Although an abnormal relationship between renal perfusion pressure and renal sodium excretion has been identified in every type of hypertension where it has been sought, factors responsible for this effect are still unclear.2. Nitric oxide (NO) is produced within the kidney and plays an important role in the control of many intrarenal processes that regulate the renal response to changes in perfusion pressure and, thus, help determine systemic vascular volume and blood pressure. Numerous studies have shown that long‐term inhibition of NO synthesis results in a chronic hypertensive shift in renal pressure natriuresis.3. Recent studies have shown that certain animal models of genetic hypertension and forms of human hypertension areas are associated with a decrease in NO synthesis. Reductions in NO synthesis reduce renal sodium excretory function, not only through direct actions on the renal vasculature, but through modulation of other vasoconstrictor processes and through direct and indirect alterations in tubular sodium transport.4. The causes and consequences of the disregulation of NO in hypertension and other renal disease processes remain an important area of investigation.
G02 AND Gi3 PROTEINS MEDIATE THE ACTION OF SOMATOSTATIN ON MEMBRANE Ca2+ AND K+ CURRENTS IN OVINE PITUITARY SOMATOTROPHS
Authors: Chen Chen 
Published: June 2007

SUMMARY1. Growth hormone (GH) secretion from the anterior pituitary gland is mainly regulated by hypothalamic GH‐releasing hormone (GHRH) and somatostatin (SRIF). Somatostatin reduces both spontaneous and GHRH‐stimulated GH secretion.2. Exocytosis of GH is mainly determined by the intracellular free Ca2+ concentration ([Ca2+]i), which is regulated by the influx of Ca2+ via membrane Ca2+ channels. Somatostatin reduces the influx of Ca2+ through two separate mechanisms, namely a direct action on Ca2+ channels and an indirect action on membrane potentials through the activation of K+ channels.3. In the present experiments, somatotroph‐enriched cells were obtained from the ovine pituitary gland by means of collagenase dissociation and Percoll‐gradient centrifugation. Further identification was based on the effect of SRIF (10 nmol/L) on Ca2+ or K+ currents.4. A significant reduction in Ca2+ currents and an increase in K+ currents was obtained in response to local application of SRIF (10 nmol/L), but vehicle application had no effect. The responses of Ca2+ and K+ currents to SRIF were reversible after removal of SRIF.5. Dialysis of GTP‐λ‐s (200 μmol/L) abolished the recovery phase of K+ current response to SRIF after its removal, whereas GDP‐β‐s (200 μmol/L) totally blocked the response. Pretreatment of the cells with pertussis toxin (100 nmol/L) overnight abolished the Ca2+ current response to SRIF.6. Intracellular dialysis of antibodies to αo, α1_3, ai1‐2 and ai3summits of the G‐proteins into cells via whole‐cell patch‐clamp pipettes was confirmed by immunofluorescent staining of the antibodies.7. Dialysis of anti‐ai1‐3 or anti‐@aLi3 antibodies significantly attenuated the increase in the K+ current in response to 10 nmol/L SRIF, whereas neither anti‐αo nor anti‐αi_2 antibodies diminished the effect of SRIF on the K+ current.8. Dialysis of anti‐αo antibodies significantly attenuated the reduction in the Ca2+ current that was obtained upon application of 10 nmol/L SRIF. Neither anti‐αi‐2 nor anti‐αi3 antibody dialysis diminished the effect of SRIF on the Ca2+ current.9. Dialysis of the ao common antisense oligonucleotides (ASm) but not the αi3 AS significantly diminished the inhibitory effect of SRIF on the Ca2+ current. This effect of ao ASm dialysis occurred at 12 h incubation after dialysis, reaching a maximal level at 48 h and partially recovering at 72 h incubation. Antisense oligonucleotides specific for αo1 (αo1 AS) or αo2(α02 AS) were dialysed into somatotrophs and only αo2 AS significantly attenuated the inhibition of SRIF on the Ca2+ current.10. It is concluded that the Gi3 protein mediates the effect of SRIF on the K+ current and that the G02 protein mediates the effect of SRIF on the Ca2+ current in primary cultured ovine somatotrophs.