Publications by authors named "Peart W"

1. Plasma sodium concentration may influence renal sodium excretion. We have examined the possibility that the fall in plasma sodium that occurs during salt restriction in man might be an important stimulus for renal sodium conservation.

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1. We have previously described a progressive antidiuresis in response to low-dose vasopressin infusion during salt restriction in man, despite stable or even declining plasma vasopressin concentration. In the present study we examine the hypothesis that renal sensitivity to the antidiuretic effect of arginine vasopressin may be enhanced by salt restriction.

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1. We have studied the response of six patients with cranial diabetes insipidus and six age-matched control subjects to dietary sodium restriction during constant administration of the synthetic vasopressin analogue desamino-[8-D-arginine]vasopressin. 2.

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1. A diuresis occurs within the first 36h of salt restriction. A decline in plasma arginine vasopressin concentration may contribute to both the diuresis and antinatriuresis.

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Background: An earlier prospective study reported an association between high levels of plasma renin activity (as measured by the renin-sodium profile) and the incidence of myocardial infarction in patients with hypertension. We have investigated the relation between plasma renin activity and ischemic heart disease in the Northwick Park Heart Study.

Methods: The study included 803 white men 40 to 64 years of age selected from industrial workers in London.

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1. The effects of change from a high to low sodium diet upon renal sodium and water excretion and hormone responses were studied in patients with dissociated sympathetic control (DS, tetraplegic) and controls with sympathetic control largely intact (IS, paraplegic). 2.

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Evolution of renin.

Hypertension

November 1991

After the development of blood pressure measurements in humans, the association of high blood pressure with renal disease was established. Injection of extracts of various organs in an attempt to replace their secretions was common in the 19th century, and it was therefore natural for Tigerstedt and Bergman to investigate the effects of renal extracts. In this way, they discovered renin.

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The contribution of neurogenic mechanisms in maintaining hypertension was investigated in 13 patients with unilateral renal artery stenosis (twelve with normal, one with grossly elevated plasma renin levels) by determining the haemodynamic and hormonal responses to the centrally acting sympatholytic agent, clonidine. The same patients were studied after captopril to determine the dependency of their blood pressure on the direct peripheral effects of angiotensin-II. Sixteen patients with essential hypertension (normal plasma renin) were additionally studied after clonidine.

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Background: Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated.

Methods And Results: The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate.

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Patients with ileostomies show an early diuresis when sodium restricted; this, together with an obligatory ileal sodium loss, predisposes them to severe salt and water depletion. The role of arginine vasopressin in this circumstance and whether it is natriuretic, or antinatriuretic, is unclear. There is also controversy over its likely effect on small bowel fluid reabsorption.

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1. The fall in renal sodium excretion after dietary sodium restriction is prompt and reproducible. The importance of increased aldosterone secretion during the early phase (within 48 h) of this response is unclear.

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Objective: To demonstrate the magnitude, timing, and cause of changes in blood pressure that occur in migrants from a low blood pressure population on moving to an urban area.

Design: A controlled longitudinal observational study of migrants as soon after migration as possible and follow up at three, six, 12, 18, and 24 months after migration. A cohort of controls living in a rural area who were matched for age, sex, and locality were also observed at the same periods.

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1. To investigate the contribution of sedation to the cardiovascular effects induced by clonidine, we studied patients with essential hypertension on two separate occasions when similar levels of sedation were induced by clonidine and nitrazepam. 2.

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We have determined the haemodynamic responses to a balanced liquid meal in eight normal subjects, before and after administration of the somatostatin analogue, Octreotide (SMS 201-995), which inhibits the release of gastrointestinal peptides. In the absence of Octreotide ingestion of the meal caused a marked increase in superior mesenteric artery (SMA) blood flow. Blood pressure was maintained, presumably by a compensatory rise in cardiac output and forearm vascular resistance.

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Human fetal lung homogenates contain an inactive form of renin which may be revealed by trypsin treatment. When activated, this form of renin has some biochemical similarities with fetal kidney renin: the pH optimum of fetal lung renin is approximately 6.5; it is bound by Affigel Blue affinity chromatography resin; and is inhibited by a monoclonal antibody (R-3-36-16) raised to human kidney renin.

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We have studied the haemodynamic, hormonal and urinary effects of postural change in 6 tetraplegic patients, 6 paraplegic patients and 6 normal subjects. Measurements of blood pressure and heart rate, plasma renin activity, plasma aldosterone, urine volume and electrolyte excretion were made for 60 minutes while sitting and 60 minutes while recumbent. In tetraplegics the blood pressure was lower when sitting and rose during recumbency, unlike paraplegics and normal subjects.

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1. The effect of intravenous vasoactive intestinal peptide (VIP, 6 pmol/kg per min) on renal function in six patients with cirrhosis of the liver was examined. 2.

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We studied the haemodynamic effects of clonidine (2 micrograms/kg/iv) in 7 tetraplegics and 7 normal subjects. Measurements of blood pressure, stroke volume, cardiac output and digital (finger) skin blood flow were made before and after clonidine for 60 minutes. Blood pressure, stroke volume and cardiac output did not fall in tetraplegics, unlike normals.

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The authors have used a sensitive alkaline phosphatase-anti-alkaline-phosphatase immunohistochemical method to examine 28 human pulmonary carcinomas for the presence of renin. Immunoreactive renin was found in 23 (82%) cases. Specific staining was always associated with small vessels in the stroma of the tumor or in adjacent areas of inflamed fibrous tissue.

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Evidence from studies in both animals and in tetraplegics with complete cervical spinal cord transection and preganglionic lesion, indicates that clonidine lowers blood pressure predominantly by a centrally mediated action. We have investigated the haemodynamic basis of this action and performed additional studies in patients with unilateral brachial plexus injury and postganglionic lesions, to further determine the site and mechanism of its action. Blood pressure fell after clonidine in normal subjects but not in tetraplegics.

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Renal vascular resistance (RVR) was related to intrarenal release of renin (RR) and angiotensin II (ANG II) during increases in plasma osmolality (Posmol) or chloride (PCl). Intrarenal infusions of 1.232 M solutions given to in situ kidneys increased Posmol by 7-18%.

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The peptide hormone neurotensin (NT) is found mainly in gut endocrine cells of the ileum, but has also been identified as a putative neurotransmitter in the central and peripheral nervous systems. It may have a dual role as a circulating gastrointestinal hormone and peripheral neurotransmitter. Its predominant effects are to reduce oesophageal sphincter tone, inhibit gastric secretion and emptying and inhibit intestinal motility, but stimulate intestinal and pancreatic exocrine secretion; NT-like immunoreactivity has been found in kidney and therefore NT may influence renal function.

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Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-1 min-1 pentagastrin; 5, 50 and 450 pmol kg-1 min-1 CCK8).

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The mechanisms of the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) are unclear. Rabbit studies suggest that VIP-induced tachycardia is largely beta-adrenoceptor mediated, but that the renin response may be partially prostaglandin-dependent. To examine the relative importance of prostaglandins and reflex sympathetic activation in the haemodynamic and renin responses to VIP infusion in man, we completed two randomised single-blind crossover studies in two groups of six healthy male volunteers (aged 24-35 years).

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