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Biomedical subjects

M J Peach

Publications and source records attributed to M J Peach.

At least 109 records · Page 6Linked to original sources
PubMed1984

Angiotensin II mediates increased small intestinal fluid absorption with extracellular volume depletion in the rat.

The purpose of this study was to determine if the increase in small intestinal fluid absorption observed after extracellular fluid (ECF) reduction is mediated by angiotensin II (AII). Infusion of AII at doses that increase plasma levels of the hormone within the physiological range stimulates jejunal fluid absorption. In contrast, at pharmacological doses that result in plasma AII levels unlikely to be encountered normally, the hormone inhibits absorption and/or stimulates jejunal secretion. The AII stimulation of jejunal fluid absorption is potentiated by nephrectomy, suggesting that the endogenous levels of AII are related to and have an important role in regulation of the cellular level of its own receptors. Extracellular volume reduction as a result of sodium depletion, nonhypotensive hemorrhage, or water deprivation increases jejunal fluid absorption 30-40% above control values. This increase in jejunal absorption after ECF reduction is not affected by adrenalectomy, but is abolished by nephrectomy, either alone or in combination with adrenalectomy. Captopril, prazosin, and peripheral sympathectomy also abolish the increase in jejunal absorption following ECF depletion. It is suggested that AII is generated after ECF reduction and increases jejunal fluid absorption by facilitating the release of norepinephrine from enteric sympathetic nerves. Thus, AII is a physiologically important mediator of jejunal fluid absorption.

Adrenalectomy↗
PubMed1984

Temperature sensitivity of angiotensin-induced inotropic effects.

Temperatures in the range of 30 to 37 degrees C were examined for effects on angiotensin (Ang) peptide-induced inotropic actions in rabbit isolated aortic rings and left atria. Both transmurally-stimulated and punctate-stimulated atria were employed to examine neurogenic and direct cardiac actions of the Ang, respectively. The peptides examined were Ang II, Ang III, and sarcosyl1-Ang II. Ang III was more potent at 33 degrees C than at 37 degrees C in the transmurally stimulated atria, in which the Ang III concentration-response curve was shifted roughly 10-fold to the left at 33 degrees C in comparison to 37 degrees C. Sarcosyl1-Ang II responses were maximal at 37 degrees C and significantly reduced at lower temperatures in aortic rings (30 degrees C) and in transmurally stimulated atria (30 and 33 degrees C). Ang II actions were not significantly altered by temperature changes in the 30 to 37 degrees C range except in transmurally stimulated atria, in which angiotensin II was more potent at 30 degrees C than at 33 degrees C. The results indicate that relatively small temperature alterations can profoundly affect potency ratios and maximal responses among the angiotensin peptides particularly when the angiotensin response is mediated in part by activation of sympathetic neurons, as in the transmurally stimulated atria. The data are consistent with either different mechanisms of cellular stimulation or multiple populations of receptors for the angiotensins. The greater effect of temperature alterations on angiotensin responses in the transmurally stimulated atria suggests that the peptides influence sympathetic nerves and cardiac or smooth muscle differently.

Angiotensin II↗
PubMed1984

Renovascular hypertension: effect of halothane and enflurane.

Male Wistar rats were anesthetized at 6 weeks of age and a silver clip placed around the renal artery to produce renovascular hypertension. The rats were allowed to grow on a normal sodium diet for the next 6-9 weeks. Using diethyl ether anesthesia, arterial and venous cannulae were placed and the animals allowed to awaken in restraining cages. The group of rats was divided into three groups: awake (n = 7), halothane 1.3 vol% (n = 9), and enflurane 2.2 vol% (n = 8). The protocol consisted of a 1-h control awake period, 1 h of stable anesthesia (one group received no anesthesia), and 30-min iv infusion of saralasin, a competitive inhibitor of angiotensin II. Plasma renin activity (PRA) and plasma catecholamines were measured after 1 h of stable anesthesia and after the saralasin infusion. In additional rats treated identically, radiolabelled microspheres were used to measure cardiac output and regional blood flows during halothane (n = 7) or enflurane (n = 6) anesthesia. Principal responses were as follows: mean arterial pressure (MAP) was 193 +/- 4 mmHg awake and decreased to 114 +/- 3 mmHg and 135 +/- 3 mmHg with halothane and enflurane, respectively. Saralasin decreased MAP in the awake group to 176 +/- 3 mmHg and to 69 +/- 3 mmHg and 96 +/- 5 mmHg with halothane and enflurane, respectively. PRA in the awake rats was 7.24 +/- 1.3 ng X ml-1 X h-1. PRA increased with halothane but decreased with enflurane. Plasma catecholamines were decreased markedly by saralasin and by both anesthetic agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1983

Granulocytes and phorbol myristate acetate increase permeability to albumin of cultured endothelial monolayers and isolated perfused lungs. Role of oxygen radicals and granulocyte adherence.

Human granulocytes and phorbol myristate acetate (PMA) increased permeability to albumin of monolayers of cultured endothelial cells grown on micropore filters. Granulocytes from a patient with chronic granulomatous disease and PMA did not increase endothelial permeability to albumin, demonstrating that the increase in permeability is dependent on granulocyte-derived oxygen radicals. When granulocytes were separated from the endothelial cells by a micropore filter, granulocytes and PMA no longer increased endothelial permeability to albumin, demonstrating that PMA-stimulated granulocytes must be closely approximated to endothelial cells to increase endothelial permeability. The relevance of these in vitro findings to an intact microvasculature was confirmed by demonstrating that agents that reduce granulocyte adherence to endothelium reduce edema formed in isolated lungs by granulocytes and PMA, an oxygen radical dependent process. Pretreatment of granulocytes with cytochalasin B or addition of 2% dextran to isolated lung perfusates reduced granulocyte adherence and markedly reduced edema formation in isolated lungs. These studies demonstrate that PMA-stimulated granulocytes must be closely apposed to endothelial cells to increase endothelial permeability through an oxygen-radical-dependent mechanism, and they suggest that reduction of granulocyte adherence may protect against granulocyte-dependent edema.

Animals↗
PubMed1983

Control of renal function by intrarenal angiotensin II.

The purpose of this study was to determine if endogenous angiotensin II affects renal function in conscious dogs after sodium restriction. Intrarenal infusion of the angiotensin receptor antagonist saralasin at doses between 0.13 and 2.5 micrograms/kg X min rapidly attenuated pressor responses produced by systemic injections of angiotensin I over a 90-min period. In contrast, intrarenal infusion of the peptide antagonist at 0.07 microgram/ kg X min did not alter the pressor response to injected angiotensin I. Infusion of angiotensin II into the kidney at 0.1 microgram/min reduced urine output by 50% and was totally inhibited by simultaneous infusion of 0.07 micrograms/kg X min saralasin. Intrarenal infusion of saralasin at 0.07 micrograms/kg X min into sodium-restricted conscious dogs increased effective renal plasma flow, glomerular filtration rate, and sodium, potassium and water excretion, whereas urine osmolarity and free water formation were unchanged. These data demonstrate that saralasin can be effectively confined to the renal mass after intrarenal infusion at a dose capable of inhibiting angiotensin action and that endogenous angiotensin plays an important role in maintaining renal function after sodium restriction.

Angiotensin I↗
PubMed1983

Possible mechanism of action of metoclopramide-induced aldosterone secretion: in vivo and in vitro studies in the sheep.

To define further the mechanism by which metoclopramide, a dopamine antagonist, stimulates aldosterone secretion, seven lambs were injected iv with metoclopramide during a constant infusion of 5% dextrose in water and again during a constant infusion of trimethapan, a ganglionic blocker. In addition, suspensions of adrenal zona glomerulosa cells from the lambs were incubated in vitro in the presence of various concentrations of metoclopramide and known secretagogues. Plasma aldosterone concentrations increased in response to both metoclopramide and trimethaphan. However, during the trimethaphan infusion, no further increase in plasma aldosterone concentrations occurred after metaclopramide injection. In vitro, aldosterone concentrations in the zona glomerulosa cell suspensions increased in the presence of ACTH, potassium, and angiotensin II, but no increase in aldosterone concentration occurred in the presence of metoclopramide. These results suggest that in the sheep, metoclopramide stimulates aldosterone secretion by an indirect mechanism. This mechanism may involve the autonomic nervous system, since ganglionic blockade appeared to abolish the aldosterone response to metoclopramide.

Adrenal Glands↗
PubMed1983

Endothelium-dependent relaxation of rabbit aorta. I. Relaxation stimulated by arachidonic acid.

Vascular responses to the addition of arachidonic acid (AA) were characterized in rings of rabbit thoracic aorta. In preparations which were precontracted to a stable plateau by 10(-7) M phenylephrine, AA (10-100 microM) elicited transient relaxation if the endothelium was intact. The same concentrations of AA only contracted tissues in which the endothelium was purposely disrupted. Indomethacin pretreatment (14 microM, 30 min) potentiated the relaxation response in intact rings. Under these conditions, relaxation in response to 100 microM AA was 32(+/- 3)% of the tension stimulated by 10(-7) M phenylephrine. Preincubation with 5,8,11,14-eicosatetraynoic acid (50 microM) or nordihydroguaiaretic acid (25 microM) completely prevented AA-induced relaxation. Contractile responses to AA were examined in rings lacking pre-existing active tension. AA (3-100 microM) elicited rapidly developing and somewhat transient contractions in rings with endothelium. Slow developing contractions which were significantly smaller in magnitude were observed in rings lacking endothelium. Indomethacin or 5,8,11,14-eicosatetraynoic acid pretreatment inhibited AA-stimulated contractions both in intact and de-endothelialized tissues. Nordihydroguaiaretic acid pretreatment had no effect on contractile responses in rings lacking endothelium and slightly potentiated responses in intact rings. We conclude that endothelium-dependent relaxation of rabbit aorta by AA is mediated by a noncyclooxygenase metabolite(s). Contractile responses are mediated by cyclooxygenase metabolites, which in intact rings are derived largely from the vascular endothelium.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1983

Endothelium-dependent relaxation of rabbit aorta. II. Inhibition of relaxation stimulated by methacholine and A23187 with antagonists of arachidonic acid metabolism.

Methacholine, A23187 and arachidonic acid (AA) relax segments of rabbit thoracic aorta via mechanisms which are dependent on an intact endothelium. Relaxation stimulated by AA was previously found by us to be antagonized by eicosatetraynoic acid and nordihydroguaiaretic acid, but not indomethacin. The purpose of the present investigation was to determine the effects of several inhibitors of AA metabolism on endothelium-dependent relaxation stimulated by methacholine and A23187 in rings of rabbit thoracic aorta. Relaxation in response to methacholine and A23187 was: 1) not affected by indomethacin pretreatment (20 microM, 30 min); 2) inhibited by 50 microM eicosatetraynoic acid pretreatment, 53 and 33%, respectively; and 3) inhibited in a dose-dependent manner by nordihydroguaiaretic acid (10-50 microM) with complete inhibition occurring after 25 and 50 microM pretreatment, respectively. Methacholine-induced relaxation was completely blocked by 10 microM quinacrine (QUIN), whereas A23187-stimulated responses were not significantly affected. QUIN (10 microM) antagonized methacholine-stimulated contractile responses in a noncompetitive manner in rings devoid of endothelium. QUIN may interfere with activation via muscarinic receptors, complicating interpretation of its inhibitory effects. Eicosatetraynoic acid (50 microM), nordihydroguairetic acid (50 microM) and QUIN (10 microM) do not exert significant inhibitory effects at the level of smooth muscle relaxation mechanisms as isoproterenol-induced relaxation was resistant to inhibition by these agents. We conclude that methacholine and A23187 relax rabbit aorta by mechanisms which require intact endothelium and involve noncyclooxygenase metabolites of AA.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1982

Role of endothelial cell cytoskeleton in control of endothelial permeability.

Increased permeability of the pulmonary microvasculature is felt to cause acute noncardiogenic lung edema, and histological studies of edematous lungs show gaps between apparently healthy endothelial cells. To determine whether alterations in endothelial cell cytoskeletons would alter endothelial permeability, we exposed monolayers of pulmonary artery endothelial cells grown on micropore filters to cytochalasin B or D. Cytochalasin exposed monolayers demonstrated a 2- to 3-fold increase in endothelial permeability that was readily reversible by washing the monolayers free of cytochalasins. Parallel phase contrast and fluorescence microscopy demonstrated retraction of cell cytoplasm and disruption of bundles of microfilaments in cytochalasin exposed cells. These changes also were readily reversed after washing the cells free from cytochalasins. To test the relevance of these findings to an in situ microvasculature, we added cytochalasin B to the perfusate of isolated rabbit lungs and observed that cytochalasin B caused a high permeability lung edema. These studies suggest that endothelial cell cytoskeletons may be important determinants of endothelial permeability.

Animals↗
PubMed1981

Response of rat jejunum to angiotensin II: role of norepinephrine and prostaglandins.

At low doses, angiotensin II (AII) stimulates jejunal sodium and water absorption in the pentobarbital sodium-anesthetized rat. This response to the hormone can be blocked by cycloheximide and has a rapid onset and decay, indicating that any protein involved must have a short half-life and/or fast turnover. At high doses, AII inhibits jejunal absorption by a process that does not involve protein synthesis and has a rapid onset but slow decay. The AII-induced inhibition of water absorption can be abolished, and a net stimulation ensues after pretreatment of the animals with meclofenamate or indomethacin, suggesting that at high doses AII stimulates intestinal prostaglandin biosynthesis. The AII analogue, [Sar1,Leu8]AII, significantly stimulated jejunal water absorption and was devoid of any inhibitory response at any dose administered. Simultaneous infusion of low doses of [Sar1,Leu8]AII and AII resulted in a stimulation of water transport, while simultaneous infusion of high dose [Sar1,Leu8]AII and AII also stimulated water absorption. It is suggested that the AII analogue is a full agonist with regard to stimulation of jejunal transfer but antagonizes the inhibitory response to high doses of AII. A model consistent with these data is discussed.

Angiotensin II↗
PubMed1981

Ontogeny of blood pressure and the renin-angiotensin-aldosterone system. Sequential studies in the newborn lamb.

To test the hypothesis that the rise in arterial pressure occurring with maturation is due to an increase in the vascular responsiveness to angiotensin II, sequential cumulative doses of angiotensin II were infused intravenously into chronically catheterized newborn lambs maintained on a constant, weight-adjusted sodium intake from birth to 8 weeks of age. Basal mean arterial pressure correlated with both age and weight, but age was a stronger determinant of mean arterial pressure than was weight. No change in the mean arterial pressure response to angiotensin II occurred with maturation. Basal plasma renin activity and plasma aldosterone concentrations were low and did not change significantly with age. Therefore, in the newborn lamb in the sodium replete state, age is a better determinant of arterial pressure than is weight. However, an age-related change in vasoconstrictor responsiveness to angiotensin II does not occur and, therefore, cannot account for the rise in arterial pressure that is observed with maturation.

Aging↗