bluuebunny/crossref_metadata_2025_split huggingface dataset:
NITRERGIC TRANSMISSION: NITRIC OXIDE AS A MEDIATOR OF NON‐ADRENERGIC, NON‐CHOLINERGIC NEURO‐EFFECTOR TRANSMISSION
Authors: Rand M. J. 
Published: June 2007

SUMMARY1. The possibility that transmission at some non‐adrenergic, non‐cholinergic (NANC) neuro‐effector junctions is mediated by nitric oxide (NO) arose from the discoveries that NO mediated the effects of nitrovasodilator drugs and that endothelium‐derived relaxing factor (EDRF) was NO or a NO‐yielding substance.2. NO donated by nitrovasodilator drugs or formed by endothelial cells activates soluble guanylate cyclase in smooth muscle and the consequent increase in cyclic guanosine monophosphate (cGMP) results in relaxation. The relaxations produced by stimulation of some NANC nerves are also due to a rise in cGMP.3. The biosynthesis of NO by oxidation of a terminal guanidino nitrogen of l‐arginine is inhibited by some NG‐substituted analogues of l‐arginine. These substances block EDRF formation by NO synthase and endothelium‐dependent vasodilatation, and the blockade is overcome by l‐arginine4. NANC relaxations in some tissues are blocked by NG‐substituted analogues of l‐arginine and restored by l‐arginine. Other agents that affect endothelium‐dependent vasodilator responses produce corresponding changes in responses to stimulation of these NANC nerves. Such observations indicate that transmission is mediated by NO: we have termed this mode of transmission nitrergic.5. There is evidence for nitrergic innervation of smooth muscle in the gastrointestinal tract, genitourinary system, trachea and some blood vessels (penile and cerebral arteries).6. The recognition of a mediator role for NO in neurotransmission calls for reconsideration of previously accepted generalizations about mechanisms of transmission.7. Studies on nitrergic transmission will provide new insights into physiological control mechanisms and pathophysiological processes and may lead to new therapeutic developments.
ATRIAL AND BRAIN NATRIURETIC PEPTIDES: SECRETION DURING EXERCISE IN PATIENTS WITH ESSENTIAL HYPERTENSION AND MODULATION BY ACUTE ANGIOTENSIN‐CONVERTING ENZYME INHIBITION
Authors: Kohno Masakazu , Horio Takeshi , Yokokawa Koji , Murakawa Koh‐ichi , Yasunari Kenichi , Kurihara Naotsugu , Takeda Tadanao 
Published: June 2007

SUMMARY1. This study examined whether brain and atrial natriuretic peptides (BNP, ANP) are secreted together through the coronary sinus from the heart, and whether plasma concentrations of BNP and ANP were affected by ergometric exercise in patients with essential hypertension. The effect of temocapril, a potent angiotensin‐converting enzyme (ACE) inhibitior, on plasma concentrations of these peptides was also examined.2. The plasma concentrations of immunoreactive (ir) BNP and ir‐ANP in the coronary sinus in seven patients with ischaemic heart disease during cardiac catheterization were far greater than values with plasma obtained at the same time from the femoral artery.3. The plasma concentrations of ir‐BNP and ir‐ANP increased with exercise and were correlated with each other. Temocapril reduced the blood pressure and slightly (but significantly) decreased the levels of both peptides at rest and during exercise.4. The results suggested that BNP and ANP were secreted together through the coronary sinus from the heart. The secretion was increased by exercise and suppressed by acute ACE inhibition. The increase in these peptides during exercise may reflect a compensatory mechanism against further elevation of blood pressure.
REGULATION OF PROXIMAL TUBULE FUNCTION BY ANGIOTENSIN
Authors: Harris Peter J. 
Published: June 2007

SUMMARY1. Independent of its effects on renal haemodynamics and glomerular filtration, angiotensin II (All) has direct actions on the proximal tubule involving transepithelial Na+, H+, HCO3‐, and water reabsorption, ammoniagenesis, gluconeogenesis and renal growth.2. The effects of AH on water and electrolyte transport are biphasic and dose‐dependent, such that low concentrations (10‐12–10‐9 mol/L) stimulate reabsorption whereas high concentrations (10‐7‐10‐6 mol/L) inhibit reabsorption. Similar dose‐response relations have been obtained for luminal and peritubular addition of AIL3. The cellular responses to All are mediated via an AT‐1 receptor coupled via G‐regulatory proteins to several parallel signal transduction pathways. Low doses inhibit the basolateral adenylate cyclase, lower intracellular cAMP and withdraw the inhibitory effect of protein kinase A on the luminal Na/H exchanger. Stimulation of this exchanger may also occur due to All‐receptor activation of phospholipase C to release diacyl glycerol, or by local transduction in the brush‐border membrane involving phospholipase A2.4. Inhibition of proximal fluid reabsorption is associated with increased intracellular Ca2+ released from intracellular stores, or entering via voltage‐sensitive channels in response to the release of inositol‐l,4,5,‐trisphosphate, or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6,‐epoxy‐eicosatrienoic acid.5. The stimulatory actions of peritubular All on proximal transport are inhibited by physiological concentrations of atrial natriuretic factor (ANF) and by parathyroid hormone (PTH).6. It is concluded that intrarenal All acts to maintain optimal matching of fluid reabsorption and filtered load in response to changes in sodium balance, as well as to promote acidification of the urine during acidosis and perhaps to potentiate tubular growth following renal injury.
SODIUM AND NORADRENALINE IN CEREBROSPINAL FLUID AND BLOOD IN SALT‐SENSITIVE AND NON‐SALT‐SENSITIVE ESSENTIAL HYPERTENSION
Authors: Kawano Yuhei , Yoshida Kaoru , Kawamura Minoru , Yoshimi Hiroki , Ashida Terunao , Abe Hitoshi , Imanishi Masahito , Kimura Genjiro , Kojima Shunichi , Kuramochi Morio , Omae Teruo 
Published: June 2007

SUMMARY1. The effects of dietary sodium on blood pressure and levels of sodium, other electrolytes and noradrenaline (NA) in the cerebrospinal fluid (CSF) and blood of 15 patients with essential hypertension were studied. The CSF and blood sampling was carried out after 7 days of a high salt intake (16–18 g/day) and after 7 days of a low salt intake (1–3 g/day).2. Blood pressure and sodium concentrations in CSF and serum were significantly higher in the high salt period than the low salt period (CSF Na+ concentration: 147.7 ± 0.4 mmol/L vs 145.3 ± 0.5 mmol/L; P < 0.001). Levels of CSF pressure and potassium or calcium concentrations were not different between the two periods. Plasma NA and plasma renin activity (PRA) were lower and CSF NA levels tended to be lower in the high salt period.3. The levels and the changes in sodium and NA in CSF were not significantly different between the salt‐sensitive (n= 8) and the non‐salt‐sensitive (n= 7) subjects, but the changes in plasma NA and PRA were smaller in the salt‐sensitive subjects.4. These results indicate that the sympathetic nervous system is less suppressed in salt‐sensitive subjects during high salt intake. This may be due to altered neural responsiveness to sodium loading rather than being greater increases in sodium concentration in the central nervous system.
SAMPLE SIZE REQUIREMENTS FOR CLINICAL TRIALS OF ISOLATED SYSTOLIC HYPERTENSION
Authors: Silagy C. A. , McNeil J. J. , McGrath B. P. 
Published: June 2007

SUMMARY1. This study investigated components of blood pressure variability in elderly subjects with isolated systolic hypertension (ISH) using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different designs.2. Eleven elderly subjects not receiving antihypertensive medication were seen on four occasions at weekly intervals. On each occasion blood pressure was measured in the clinic and then for 24 h using a non‐invasive ABPM device. Nested analysis of variance was used to calculate the ‘between subject’ and ‘between subject within occasion’ components of blood pressure variability.3. Increasing the number of readings or occasions where measurement was performed in a parallel group trial only reduced the variability substantially when the number of subjects involved was less than 50. Use of a cross‐over design substantially reduced the sample size required.4. ABPM appears most useful as a strategy for reducing sample size in parallel group trials in ISH involving small numbers of subjects measured on one occasion.
CONCURRENCE OF PRIMARY ALDOSTERONISM AND RENAL ARTERY STENOSIS
Authors: Stokes Gordon S. , Monaghan Judith C. , Roche James , Grunstein Harry , Gordon Richard D. 
Published: June 2007

SUMMARY1. An unusual clinical case is described in which renal artery stenosis (RAS) was found to coexist with adrenocortical hyperplasia, resulting in hypertension.2. Partial relief of the hypertension was achieved by correction of RAS, and then further relief by extirpation of one adrenal gland affected by unilateral hyperplasia, in interventions 8 months apart.3. Biochemical features typical of primary hyperaldosteronism were observed both before and after RAS repair but were not present after unilateral adrenalectomy.4. The association of these two lesions could have occurred by chance, through genetic linkage, or by progression from RAS to tertiary aldosteronism.
FAMILIAL HYPERALDOSTERONISM TYPE II: FIVE FAMILIES WITH A NEW VARIETY OF PRIMARY ALDOSTERONISM
Authors: Stowasser Michael , Gordon Richard D. , Tunny Terry J. , Klemm Shelley A. , Finn Wendy L. , Krek Anton L. 
Published: June 2007

SUMMARY1. Thirteen patients from five families had Familial Hyperaldosteronism Type II (FH‐II), a new variety of familial primary aldosteronism not suppressible with dexamethasone that often involves adrenocortical adenoma formation.2. Five patients had solitary aldosterone‐producing adenomas, three had bilateral autonomous overproduction of aldosterone, and in five the subtype is yet to be determined.3. Comparing FH‐II patients with 88 patients with primary aldosteronism of other causes revealed no differences in mean age at presentation or at onset of hypertension, sex incidence, lowest recorded serum potassium, plasma aldosterone, plasma renin activity or adenoma size.4. Analysis of DNA in peripheral blood of patients with FH‐II, their affected and unaffected relatives, and in removed tumours is in progress in order to determine the underlying genetic defect(s) in FH‐II, perhaps an abnormality in the P‐450aldo gene (CYP11B2).5. It is recommended that hypertensive relatives of patients with primary aldosteronism should have measurements of the aldosterone/renin ratio.
EFFECT OF ENALAPRIL ON BODY SODIUM AND HANDLING OF A SODIUM CHLORIDE LOAD IN HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Ledingham J. M. , Simpson F. O. 
Published: June 2007

SUMMARY1. The effect of enalapril on handling of an Na load and on body Na during 96 h of zero Na intake was measured in hypertensive rats (GH and SHR) and their normotensive controls (N and WKY) by a whole body counting method.2. Enalapril treatment led to a greater fall in body Na in the first 24 h after the Na load (as expected from the known effect of ACE inhibition on aldosterone production) and thus to a slightly faster excretion of an amount equivalent to the load.3. Enalapril‐treated rats were unable to maintain body Na on a zero Na intake. This was also expected from the known effect on aldosterone production, though other mechanisms are not excluded. The effect was more marked in the SHR and WKY than in GH and N but there was no significant difference in this effect between the hypertensives and their respective control strains.
ISOLATION OF ADULT CARDIOMYOCYTES INITIATES A RETURN OF INOSITOL TRISPHOSPHATE PHOSPHORYLATING ACTIVITY
Authors: Woodcock Elizabeth A. , Anderson Karen 
Published: June 2007

SUMMARY1. We have previously reported that the addition of noradrenaline to [3H]‐inositol‐labelled adult rat atria or isolated perfused hearts caused the release of inositol‐1,4,5‐trisphosphate, which was metabolized by dephosphorylation to inositol‐4‐monophosphate. Inositol‐l,3,4,5‐tetrakisphosphate and its dephosphorylation products were not detected.2. In the current study, the addition of noradrenaline to [3H]‐inositol‐labelled adult rat cardiomyocytes caused the release of inositol‐1,4,5‐trisphosphate, which was metabolized in part by phosphorylation to inositol‐l,3,4,5‐tetrakisphosphate.3. These results demonstrate that the isolation and culture of rat adult cardiomyocytes initiates enhanced generation of inositol‐1,3,4,5‐tetrakisphosphate. This change would be expected to enhance the calcium response of the cells to stimulation of α1‐adrenoceptors.
INFLUENCE OF WORKLOAD ON THE ANTIHYPERTENSIVE EFFECT OF EXERCISE
Authors: Matsusaki Motonori , Ikeda Masaharu , Tashiro Eiichiro , Koga Manabu , Miura Shin‐ichiro , Ideishi Munehito , Tanaka Hiroaki , Shindo Munehiro , Arakawa Kikuo 
Published: June 2007

b1. The relation between workload and the antihypertensive effect of exercise therapy in hypertensive patients, and the mechanism of that effect, were investigated.2. Twenty‐six patients participated in the study and were randomly assigned to 10 weeks of either low or high workload exercise. In the low workload group, 16 mild hypertensive patients were treated with bicycle ergometer exercise at approximately 50% of their maximum oxygen consumption (V̇O2max) for 60 min three times a week for 10 weeks. In the high workload group, 10 mild hypertensive patients exercised on the same schedule, but at approximately 75% of V̇O2max.3. After 10 weeks of exercise, the low workload group had significantly lower systolic (9 mmHg), mean (6 mmHg) and diastolic (6 mmHg) blood pressures. In the high workload group, decreases in systolic (3 mmHg), mean (4 mmHg) and diastolic (5 mmHg) blood pressure were not statistically significant.4. In the low workload group, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 7. Cardiac index and plasma norepinephrine tended to decrease. In the high workload group, plasma norepinephrine and the renin‐angiotensin system were transiently stimulated after 4 weeks of exercise. Stroke volume significantly increased (+26.4%) after 10 weeks of high workload exercise.5. Based on these results and better patient compliance with the exercise programme in the low workload group than in the high workload group, low workload exercise therapy was recommended to mild hypertensive patients.
THE EFFECT OF GRADED HAEMORRHAGE ON ERYTHROPOIETIN PRODUCTION IN THE IMMATURE OVINE FOETUS
Authors: Moritz Karen M. , Wintour Marelyn 
Published: June 2007

SUMMARY1. Basal and haemorrhage‐stimulated erythropoietin (Epo) and ACTH levels were measured in the chronically cannulated immature ovine foetus (< 125 days) by radio immunoassay (RIA).2. Basal erythropoietin levels were found to be higher than those previously reported in the late gestation (> 130 days) ovine foetus, but were lower than those observed in the neonatal lamb.3. In control foetuses (Protocol 1) the small degree of haemorrhage associated with the sampling procedure increased the plasma Epo values from 11.4 ± 3.0 (n= 5) mU/mL to 23.8±4.3 mU/mL at 24 h (mean ± s.e.m.). There was a significant monotonic increase with time (F= 16.4; d.f. 1,19; P= 0.001). An initial haemorrhage of approximately 10% blood volume (Protocol 2) increased plasma Epo values from 7.3±2.3 to 24.2 ± 7.1 mU/mL(n= 3).4. Haemorrhage of 20% fetal blood volume (Protocol 3) produced an increase in plasma Epo from 9.3±1.7 to 54.7 ± 15.5 mU/mL at 6 hand to 57.6 ± 7.3 mU/mLat24 h n= 5). By repeated measures ANOVA, the effect of the 20% haemorrhage was significant when compared with the control group (F= 7.32, d.f. 2, 16, P= 0.006). There was a significantly greater decrease in haematocrit (F= 6.7, d.f. 2, 20, P= 0.004) and haemoglobin (F= 5.0, d.f. 2, 20, P= 0.013) in animals of Protocol 3 than in those of Protocol 1.5. Fetal blood gases and plasma adrenocorticotropic hormone (ACTH) did not alter with haemorrhage, indicating the tolerance of the foetus to this degree of haemorrhage.
INHIBITION OF NITRIC OXIDE SYNTHASE SPECIFICALLY ENHANCES ADRENERGIC VASOCONSTRICTION IN RABBITS
Authors: Du Z‐Y. , Dusting G. J. , Woodman O. L. 
Published: June 2007

SUMMARY1. The effect of inhibition of nitric oxide biosynthesis using N‐nitro‐l‐arginine (NOLA) was examined in conscious rabbits and rabbit isolated aortae.2. In autonomically blocked conscious rabbits intravenous infusion of NOLA (15 mg/kg) significantly increased arterial pressure and hindlimb vascular resistance but did not affect heart rate. Depressor and hindlimb vasodilator responses to acetylcholine (3–12 μg/kg per min) were significantly attenuated in the presence of NOLA. In contrast, NOLA significantly enhanced responses to intravenous infusion of glyceryl trinitrate (10–40 Mg/kg per min) in vivo.3. Infusion of noradrenaline (1–4 μg/kg per min) or the release of neuronal noradrenaline in response to the infusion of tyramine (80–320 Mg/kg per min) increased arterial pressure and hindlimb vascular resistance in autonomically blocked conscious rabbits. After the administration of NOLA, the vasoconstrictor responses to both noradrenaline and tyramine were significantly enhanced.4. In isolated rabbit aortae, NOLA (10 μmol/L) significantly impaired relaxant responses to acetylcholine but did not affect responses to glyceryl trinitrate. NOLA enhanced contractile responses to the adrenoceptor agonists noradrenaline and phenylephrine but did not affect the contractile responses to the thromboxane‐mimetic U46619.5. These data indicate that in autonomically blocked conscious rabbits, NOLA causes systemic vasoconstriction, impairs dilator responses to acetylcholine and enhances dilator responses to glyceryl trinitrate. In addition, NOLA enhances constrictor responses to both exogenous and neuronally‐released noradrenaline. These results suggest that nitric oxide is important in the regulation of normal vascular tone and in the modulation of vascular responses to vasodilator and vasoconstrictor agents.
NERVE GROWTH FACTOR mRNA CONTENT PARALLELS ALTERED SYMPATHETIC INNERVATION IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Falckh Patrick H. , Harkin Louise A. , Head Richard J. 
Published: June 2007

SUMMARY1. In order to explore the mechanisms responsible for the hypernoradrenergic innervation of the vasculature in the spontaneously hypertensive rat (SHR) the tissue content of nerve growth factor messenger ribonucleic acid (NGFmRNA) was examined.2. The concentration of NGFmRNA was markedly elevated in mesenteric veins obtained from SHR when compared with the contents of NGFmRNA in veins from Wistar Kyoto rats (WKY).3. The NGFmRNA content of kidneys was greater in SHR when compared with the levels present in WKY rats for 10‐ and 43‐day‐old animals.4. In contrast to the pattern observed for veins and kidneys, the NGFmRNA content of SHR hearts was smaller than those present in hearts from WKY rats for 2, 10 and 43‐day‐old animals.5. The results demonstrate that tissues with enhanced innervation (the kidney and mesenteric vasculature) in SHR are associated with an enhanced expression of NGFmRNA. In contrast, the heart, which does not display an enhanced sympathetic innervation in the SHR, does not have an increased expression of NGFmRNA.6. It is suggested that in the SHR there is a tight relationship between hypernoradrenergic innervation in the vasculature and gene expression for NGFmRNA.
l‐ARGININE INFUSION INDUCES HYPOTENSION AND DIURESIS/NATRIURESIS WITH CONCOMITANT INCREASED URINARY EXCRETION OF NITRITE/NITRATE AND CYCLIC GMP IN HUMANS
Authors: Kanno Kazuo , Hirata Yukio , Emori Toshiaki , Ohta Kazuki , Eguchi Satoru , Imai Taihei , Marumo Fumiaki 
Published: June 2007

SUMMARY1. The vascular endothelium produces endothelium‐derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of l‐arginine (l‐Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para‐aminohippuric acid (PAH) and inulin was studied in five normal subjects.2. Infusion of l‐Arg (30 g) caused a significant fall in MBP (–8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters.3. Neither l‐Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7‐fold) and after (1.9‐fold) l‐Arg infusion, but only slightly (1.3‐fold) during saline infusion.4. Urine flow increased more remarkably following l‐Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after l‐Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary NOx excretion showed positive correlations with urinary flow (r= 0.69, P < 0.001) and with urinary cGMP excretion (r= 0.60, P < 0.01). PAH clearance showed significant increase by l‐Arg infusion, while no significant change of inulin clearance was observed.5. These date suggest that infusion of l‐Arg causes hypotension and diuresis/natriuresis associated with increase in renal plasma flow, possibly via the formation of endogenous EDRF in man.
REMODELLING OF THE VASCULAR SYSTEM IN RESPONSE TO HYPERTENSION AND DRUG THERAPY
Authors: Levy B. I. , Safar M. E. 
Published: June 2007

SUMMARY1. Arterial remodelling is an important mechanism in the pathophysiology of hypertension and its complications, being involved in the decrease of vascular reserve, the autoregulation of cerebral blood flow and the development of atherosclerosis. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth‐promoting substances. Based on these data, the effects of perindopril, a potent and long‐lasting angiotensin‐converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall have been studied in animal models of hypertension. Perindopril completely reversed the aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats and in spontaneously hypertensive rats. The effect of perindopril was consistent with the potent inhibition of vascular ACE, and emphasized the potential role of angiotensin II as a vascular growth modulator. Whether the time constant of remodelling is similar or not in the heart and large vessels remains an important question that requires further investigation.