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Biomedical subjects

M J Peach

Publications and source records attributed to M J Peach.

At least 127 records · Page 7Linked to original sources
PubMed1981

Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.

The purpose of this study was to determine the locus of interaction of angiotensin peptides with the sympathetic nervous system leading to alterations in jejunal sodium and water transport. At low physiological doses, angiotensin II (AII) stimulates jejunal sodium and water absorption, while at high doses peptide inhibits absorption and/or stimulates secretion. Both the stimulation of jejunal transport and the inhibition of absorption were expressed in adrenalectomized rats. However, the stimulation of jejunal water absorption was abolished and a potentiated inhibition of transport was expressed in peripherally sympathectomized rats (intact adrenal medulla) and in normal rats after administration of guanethadine, phentolamine, and prazosin. The angiotensin analog (Sar1 Leu8)-AII has low efficacy and is a potent competitive antagonist of the parent peptide in pressor and myotropic systems, but is a full agonist with even greater potency than AII in stimulating jejunal transport. The increased water transport in response to (Sar1 Leu8)-AII is not secondary to enhanced renal renin release, as the analog also stimulated jejunal transport in the presence of captopril and after bilateral nephrectomy. The stimulation of absorption in response to (Sar1 Leu8)-AII alone or together with AII was abolished by phentolamine. These data demonstrate that AII-increased intestinal absorption is secondary to the release of norepinephrine from nerve endings in the jejunum and that AII inhibition of absorption is not mediated by the sympathetic nervous system. The analog (Sar1 Leu8)-AII is a full agonist in the stimulation of jejunal transport (increased norepinephrine release), but antagonizes the inhibitory response to high doses of AII. Angiotensin peptides are potent modulators of intestinal sodium and water absorption.

Adrenalectomy↗
PubMed1981

Demonstration of a primary antidiuretic action of angiotensin II: effects of intrarenal converting enzyme inhibition in the conscious dog.

This study was designed to determine whether angiotensin II of renal origin physiologically mediates free water production by the kidney. The effect of renal arterial infusion of the angiotensin-converting enzyme inhibitor, teprotide, on renal function was studied under conditions of hydropenia and hydration in uninephrectomized conscious dogs after 5 days of equilibration on a normal or low sodium diet. In low sodium animals, intrarenal infusion of teprotide (0.25 microgram/kg.min) after 12 h of water restriction elicited marked increases in the glomerular filtration rate (GFR) and free water formation. After 24 h of water restriction, vasopressin (10 microU/min) was infused iv to achieve an effective maximal urine concentration. Under these conditions, the inhibitor again increased the GFR and free water formation. After the production of a state of stable hydration, intrarenal infusion of teprotide also increased the GFR and free water formation. In the normal sodium animals, intrarenal infusion of the converting enzyme inhibitor (2.5 microgram/kg.min) in 12-h hydropenic dogs failed to change the GFR but increased free water formation, while the inhibitor decreased effective renal plasma flow and free water formation in normal sodium, hydrated animals. These data suggest that angiotensin II of renal origin plays an important role in the control of free water production by the kidney.

Angiotensin II↗
PubMed1981

Responses of blood pressure and angiotensin-converting enzyme activity to acute captopril administration in normotensive and hypertensive rats.

The purpose of these experiments ws to determine the dose of captopril which resulted in essentially complete blockade of tissue and plasma converting enzyme activity (CEA) and to correlate the effect of this dose of inhibitor on blood pressure and CEA in a number of normotensive and hypertensive rat models. Oral administration of captopril (0.3-10 mg/kg) induced a dose-related attenuation of CEA in plasma freshly drawn from normotensive conscious rats. After storage at -20 or 4 C before assay, both captopril-treated and untreated plasmas displayed markedly greater CEA. The converting enzyme inhibitor induced a parallel shift to the right of angiotensin I-induced blood pressure responses, reaching a 100-fold displacement of dose-dependent responses in the presence of 10 mg/kg captopril. Sixty minutes after oral administration of 10 mg/kg captopril, plasma CEA was blocked completely in all normo- and hypertensive models studied. This dose of the inhibitor reduced blood pressure in the sodium-deplete normotensive rat, the spontaneously hypertensive rat, and the initial phase two-kidney, one-clip Goldblatt rat but not in the sodium-replete normotensive rat, the spontaneously hypertensive rat, the mineralocorticoid hypertensive rat, or the chronic phase of two-kidney, one-clip Goldblatt rat. It is concluded that acute administration of captopril at a dose which results in complete blockade of plasma converting enzyme and severe attenuation of tissue converting enzyme reduces blood pressure in animals with high PRA but not in animals in which the PRA is low. (Endocrinology 108: 536, 1981)

Angiotensin I↗
PubMed1981

Changes in an electroneutral transport process mediated by angiotensin II in the rat distal colon in vivo.

The purpose of these experiments was to determine if angiotensin II mediates the stimulation of water transport in the rat distal colon via an electroneutral mechanism. Amphotericin B (36 micrograms/ml) added to the mucosal surface of the colon significantly increased potential difference (pd) and short circuit current (scc) and significantly decreased resistance. Replacement of the luminal contents of the colon with 150 mM choline chloride decreased pd and scc while resistance remained unchanged. Increased colon resistance occurred on cooling the animals. Thus both increased and decreased pd, scc, and resistance could be measured with the preparation used in this study. The distal colon in vivo is sensitive to angiotensin II since low infusions (7 pmol/kg . min) stimulate water transfer 180% above controls. Transmural pd, resistance, and scc were measured in the distal colon, while the response to the hormone was monitored by measurement of jejunal water transport in the same animals, Intravenous infusion of angiotensin II at a subpressor dose (7 pmol/kg . min) significantly stimulated jejunal water absorption in the absence of any change in transmural pd, resistance, or scc measured in the distal colon. However, infusion of a pressor dose of angiotensin II (700 pmol/kg . min) significantly inhibited jejunal water absorption but again did not alter the electrical properties of the distal colon. These data suggest that angiotensin II can stimulate and inhibit intestinal water transport via electroneutral mechanisms. Thus, the actions of this hormone contrast with that of aldosterone, which stimulates intestinal sodium and water transport by electrogenic mechanisms.

Amphotericin B↗
PubMed1980

Formation of [Des-Asp1]angiotensin I by the perfused rat lung.

Bioassay studies have indicated that angiotensin I (Ang I), but not angiotensin II (Ang II), is degraded by the intact lung. The present study was an attempt to isolate and quantify pulmonary metabolites of Ang I. The pulmonary vascular bed of the rat was isolated and perfused at 4-6 ml/min (< 20 mm Hg) with oxygenated Krebs buffer containing 5% bovine serum albumin. [3H-Leu10]Ang I (3-10 ng) was administered, and pulmonary effluent samples were collected every 15 sec for 5 min. Peptides were isolated by Dowex chromatography and separated by thin layer chromatography. 3H-labeled peptides were eluted from the thin layer chromatography plate, and the Ang I and [des-Asp1]Ang I levels were estimated by RIA. These peptides were shown to be hydrolyzed by purified converting enzyme with the release of His-3H-Leu. About 25% of the [3H]Ang I administered was isolated as [3H-des-Asp1]Ang I, and this percentage increased to 33% after treatment with teprotide. These studies clearly demonstrate that [des-Asp1]Ang I is a major pulmonary metabolite of Ang I and suggest the presence of a pulmonary aminopeptidase which hydrolyzes Ang I but not Ang II.

Angiotensin I↗
PubMed1980

Studies of the functional role of the intrarenal renin-angiotensin system.

In the kidney, renin is synthesized and stored by specialized cells in the afferent arteriole, the juxtaglomerular cells, which are derived from smooth muscle cells. The juxtaglomerular cells are more highly differentiated than ordinary smooth muscle cells and contain numerous-bound granules, the sites where renin is stored and presumably synthesized. Specialized granular epithelial cells situated in the angle between the afferent and efferent arterioles and the distal tubule comprise the macula densa. Collectively, the granular cells of the macula densa and in the wall of the afferent arteriole are termed the juxtaglomerular apparatus [1]. It has been shown repeatedly that all components of the renin-angiotensin system are present within the kidney in close association with the component structures of the juxtaglomerular apparatus [2-4]. Thus, it has been proposed that angiotensin may be formed intrarenally, and that angiotensin exerts a controlling influence on renal function through the unique anatomical structure of the juxtaglomerular apparatus, independent of changes in the systemic renin-angiotensin system. In this article, we will assess the evidence for a functional role of the intrarenal renin-angiotensin system acting as a local hormonal system in the control of renal function.

Angiotensins↗
PubMed1979

Converting-enzyme activity and pressor responses to angiotensin I and II in the rat awake and during anesthesia.

Plasma renin activity (rate of angiotensin I generation) does not increase during anesthesia with ketamine, fluroxene, halothane or enflurane in the sodium-repleted rat. However, blood pressure decreases when an angiotensin II antagonist, saralasin, is administered during halothane or enflurane anesthesia, but not during ketamine or fluroxene anesthesia. Differences in the rates of conversion of angiotensin I to angiotensin II induced by various anesthetic agents could help explain these previous findings. To determine the effects of anesthetic agents on angiotensin I conversion, experiments were performed in vitro and in vivo. The activities of rabbit pulmonary converting enzyme in the presence and absence of halothane or fluroxene were measured as rates of appearance of the dipeptide, histidyl-leucine, a product of angiotensin I hydrolysis to angiotensin II. Halothane and fluroxene did not alter conversion. Infusions of angiotensin I and angiotensin II were given to Wistar rats to construct dose-blood pressure response curves. The animals were then anesthetized with ketamine or halothane and infusions were repeated. Angiotensin I and angiotensin II induced similar blood pressure responses in awake and anesthetized rats. However, ketamine accentuated the pressor responses to angiotensin I and angiotensin II, whereas halothane depressed the responses. With the anesthetic agents studied, there is no significant effect on conversion of angiotensin I to angiotensin II either in vitro or in vivo.

Angiotensin I↗
PubMed1979

Activity of [des-aspartyl1]-angiotensin II in primary aldosteronism.

This study describes the effects of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6+/-1 to 14+/-3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33+/-8 to 65+/-13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III.Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history.

Adrenal Glands↗
PubMed1979

Structural features of angiotensin II which are important for biologic activity.

In summary, the aromatic ring of phenylalanine (COOH-terminus) is the key to the intrinsic activity with Tyr4, also involved in activation of a response. The NH2-terminal residue is a determinant of duration of action. The side chains of Tyr4 and His6 are key determinants for affinity, and the amino acids in the No. 1 and No. 2 position also contribute to receptor binding. Val3, Ile5, and Pro7 contain neutral side chains which probably establish and/or help maintain the appropriate distances among the key sidechains of Tyr4, His6, and Phe8. In other words, Val3, Ile5 (or Val), and Pro7 are key determinants of structural conformation.

Amino Acid Sequence↗
PubMed1979

Renin response to hemorrhage in awake and anesthetized rats.

Anesthetic agents have been shown to alter survival in animals subjected to hemorrhage. Since survival after hemorrhage is increased by inhibitors of the renin-angiotensin system, we asked whether anesthetic agents altered renin release during hemorrhage. We studied 33 rats which were subjected to one hour of hemorrhagic hypotension at a mean arterial pressure of 40 mm Hg. Animals were either awake or anesthetized with halothane or ketamine. Anesthesia alone did not alter plasma renin activity (PRA), whereas hemorrhage resulted in approximately a ten-fold increase in PRA in both awake and anesthetized animals. After the shed blood was returned to the animal, intravenous saralasin, an angiotensin II competitive inhibitor, produced a 21-24 mm Hg decrease in blood pressure in all animals, regardless of the severe hemorrhage is unaltered by halothane or ketamine anesthesia, that the renin-angiotensin system provides a similar amount of blood pressure support in both awake and anesthetized animals, and that the anesthetic influence on survival following severe hemorrhage does not result from anesthetic-induced alterations of the renin-angiotensin system.

Animals↗
PubMed1978

In vitro activation of the alternative pathway of complement by settled grain dust.

Settled grain dust was collected from several active grain elevators in the Superior-Duluth areas of the United States. Particle size distribution (47% less than 5 micrometer) and endotoxin contamination (429 ng/gm) of the dust were similar to those reported for the airborne parent dust. Human complement uas activated in vitro in a dose-response manner which could be quantified. This hemolytic consumption was via the alternative pathway as defined by ethylenediaminetertraacetic acid/ethylene-glycol-bis-(beta-amino-ethyl ether) N,N'-tetraacetic acid (EDTA/EGTA) differential serum chelation, factor B conversion, and complement reductions in serum from guinea pigs deficient in C4. It is proposed that continuous low-dose exposure to aerosolized, biologically active rafter dust could contribute to the respiratory insult of grain workers.

Complement Activation↗