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M J Peach

Publications and source records attributed to M J Peach.

At least 91 records · Page 5Linked to original sources
PubMed1987

Endothelium-derived relaxing factor in cultured cells.

Many vasoactive agents stimulate release of an endothelium-derived relaxing factor (EDRF). EDRF stimulates cyclic guanosine 3',5'-monophosphate (cGMP) accumulation and relaxation of vascular smooth muscle in a manner similar to that produced by sodium nitroprusside. Endothelium and vascular smooth muscle were isolated from porcine, bovine, and rat thoracic aorta. The capacity of sodium nitroprusside to stimulate cGMP accumulation in cultured bovine, porcine, and rat vascular smooth muscle was found to increase with time in culture to a maximum of 12 to 14 days after plating. In addition, bovine and porcine vascular smooth muscle, but not rat vascular smooth muscle, lost the sodium nitroprusside-stimulated cGMP response after the fifth passage. Cultured endothelial cells did not respond to endothelium-dependent vasodilators or sodium nitroprusside with increased cGMP levels. Vascular smooth muscle cells responded only to sodium nitroprusside. Mixed cultures of porcine and bovine endothelium and vascular smooth muscle and bovine endothelium and rat vascular smooth muscle responded to endothelium-dependent vasodilators with increased cGMP levels. Short-term (4 hours) coculture experiments using bovine endothelium grown on microcarriers to assess the need for long-term contact between the two cell types produced similar results. Release of EDRF from bovine endothelium was studied by loading endothelium-covered microcarrier beads into a column superfused with physiological buffer. Treatment of the column with bradykinin, the calcium ionophore A23187, melittin, and arachidonate released EDRF from the column as measured by cGMP changes in denuded aortic rings and vascular smooth muscle cells and by relaxation of rings when bathed in column effluent. The time course of cGMP changes and relaxation were similar and could be reversed by hydroquinone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Presence of angiotensinogen messenger RNA in various cultured cell lines.

The presence of angiotensinogen messenger RNA (mRNA) was assessed in total RNA extracted from hepatoma, glioma, neuroblastoma, and glioma-neuroblastoma hybrid cell lines. Total RNA from 1 X 10(7) cells was extracted, transferred to a membrane, and hybridized with a 32P-labeled, full-length (1650-base pair) rat angiotensinogen complementary DNA (cDNA). Angiotensinogen RNA sequences could be definitively detected only in hepatoma cells. Steroids were used in an attempt to increase the angiotensinogen mRNA level. Dexamethasone (2 X 10(-6) M) or 17 beta-estradiol (1 X 10(-7) M) was added to the cultures 18 to 24 hours prior to harvest. Dexamethasone treatment of the hepatoma cells resulted in a large increase in angiotensinogen mRNA, whereas estradiol had no effect. Steroids failed to induce detectable levels of angiotensinogen mRNA in total RNA from the other cell lines. That the RNA was intact was ensured by hybridizing duplicate Northern blots to a 32P-labeled actin cDNA. Actin mRNA sequences were detected in all cell lines. Blot hybridization of poly(A)+RNA resulted in the visualization of a weak angiotensinogen mRNA signal for a glioma cell line and a glioma-neuroblastoma hybrid line. However, the ability to detect angiotensinogen mRNA in a cell may depend on the phenotype expressed, which can be governed by culture conditions.

Angiotensinogen↗
PubMed1987

Renal sensitivity to angiotensin II in the conscious dog.

Local formation of angiotensin II (AII) within the kidney has been demonstrated. Changes in renal function induced by inhibitors of the renin-angiotensin system have been the basis for the postulate that AII may act as a paracrine substance in the kidney. We studied the renal action of chronic intrarenal infusions of AII at doses between 2 and 2000 fmol/kg X min in uninephrectomized conscious dogs monitored on 80 meq daily sodium intake. Exogenous AII was confined to the kidney, as demonstrated by the absence of systemic pressor and adrenal cortical responses during the intrarenal infusion. After 2 control days, each dose of AII was infused intrarenally for a period of 3 days. The smallest intrarenal dose of AII that caused significant antinatriuresis and antidiuresis was 20 fmol/kg X min. A significant reduction in urinary volume and sodium excretion occurred during the first 24 h of the infusion period and was proportionate to the amount of peptide infused. Renal escape from the antinatriuretic and antidiuretic effects of the peptide ensued on the second and third days of infusion. There were no significant changes in urinary potassium excretion, plasma renin activity (PRA), plasma aldosterone concentration, or blood pressure throughout the period of intrarenal AII administration. These data demonstrate dose-dependent direct antinatriuretic and antidiuretic actions of low AII concentrations. Escape from the sodium-retaining action of intrarenal AII occurred by 48 h and was independent of suppression of endogenous renin-angiotensin. These results indicate that AII alters renal function by direct intrarenal mechanisms.

Aldosterone↗
PubMed1987

Alpha adrenergic receptors mediate angiotensin-induced prostaglandin production in the rabbit isolated vas deferens.

The effect of alpha adrenergic receptor antagonists on concentration-dependent response to angiotensins II and III was examined in the electrically stimulated isolated rabbit vas deferens. The force generated by a nonadrenergic neural mechanism was reduced by both peptides whereas the force generated by adrenergic neural mechanisms was enhanced. Angiotensin III-induced inhibition of the nonadrenergic contraction was significantly greater than that of angiotensin II for all groups. Yohimbine (1 X 10(-4) M), an alpha-2 receptor antagonist, attenuated the depression of the nonadrenergic contraction produced by angiotensins II and III. Yohimbine (1 X 10(-5) and 1 X 10(-4) M) also significantly reduced angiotensin II-induced prostaglandin E (PGE) synthesis. Yohimbine only significantly altered the angiotensin III-induced PGE synthesis at an antagonist concentration of 1 X 10(-4) M. Rauwolscine (1 X 10(-8) and 1 X 10(-7) M) attenuated angiotensin II-induced PGE production and at a higher concentration (1 X 10(-6) M) reduced angiotensin III-induced PGE production. The alpha-1 antagonist, prazosin (1 X 10(-6) M), did not alter nonadrenergic contractile or PGE responses to either angiotensin. The alpha-2 agonist, clonidine, both inhibited the nonadrenergic neural contraction and enhanced PGE synthesis. We interpret these data to indicate that angiotensins II and III may act via separate mechanisms to induce PGE synthesis in the vas deferens, with angiotensin II effects being more dependent on norepinephrine release from adrenergic nerves.

Angiotensin II↗
PubMed1986

Correlation of cigarette-induced increase in serum nicotine levels with arginine vasopressin concentrations in the syndrome of self-induced water intoxication and psychosis (SIWIP).

Ten patients [9 men and 1 woman; mean age 42.4 +/- 8.5 (+/- SD) years] who were smokers and who suffered the complications of self-induced water intoxication and psychosis (SIWIP) (8 patients with schizophrenic disorders, 1 patient with manic-depressive illness, 1 patient with dementia) are reported. Each patient underwent serial determinations of parameters of water metabolism including plasma and urine osmolality and plasma arginine vasopressin (AVP). The syndrome of inappropriate antidiuresis (SIAD) was found in each patient. Because of the reported effect that cigarette smoking has on antidiuresis, we correlated serum nicotine (NIC) levels with plasma and urine osmolality, AVP, and 24-hour urine volume (24 degrees-UV). We found no relationship between NIC and plasma or urine osmolality, AVP, or 24 degrees-UV. In the presence of SIWIP and SIAD, we infer the limbic-hypothalamic neurotransmitters in these psychotic patients are sufficiently powerful in stimulating both compulsive water drinking and inappropriate release of AVP so as to overshadow any effects that NIC may have on water metabolism.

Adult↗
PubMed1986

Angiotensin peptides and prostaglandin E2 synthesis: modulation of neurogenic responses in the rabbit vas deferens.

Isolated rabbit vasa deferentia were used to study the neuromodulation induced by angiotensins II and III (AII and AIII) upon both phases of the electrically stimulated contraction (ESC). AIII (10(-8)-10(-7) M) was shown to inhibit the ESC at low frequencies (2-10 Hz), while AII tended to potentiate both phases. Since AIII had no effect on contractions induced by exogenous ATP (twitch, putative transmitter), or norepinephrine (NE; tonic, neurotransmitter), AIII effects were presumed to be presynaptic. AIII neuromodulation was reversed by indomethacin, and prostaglandin E2 (PGE2) mimicked the inhibitory effects of AIII on ESC. The response to AIII was blocked by [Sar1,Ala8]AII (10(-6) M), an angiotensin antagonist. AIII (10(-9)-10(-5) M) stimulated PGE2 synthesis in a concentration-dependent manner. AII (10(-9)-10(-7) M) produced a dramatic rise in PGE2 synthesis, which declined sharply at higher AII concentrations. AII increased the overflow of [3H]NE approximately 50% (P less than 0.01; in the absence of indomethacin); similar concentrations of AIII did not affect [3H]NE release. However, 4 X 10(-8) M AIII in the presence of 26 microM indomethacin significantly (P less than 0.05) increased [3H]NE overflow. Thus, AIII inhibited ESC presynaptically by stimulating PGE2 synthesis, while AII potentiated these contractions presynaptically by enhancing NE release during nerve stimulation. Despite the greater inhibitory effect of AIII on force, AII was more potent than AIII in stimulating PGE2 production.

Adenosine Triphosphate↗
PubMed1985

Psychogenic polydipsia and water intoxication--concepts that have failed.

Ten patients (8 men, 2 women; mean age 38.7 +/- 8.1 years), 7 of whom had schizophrenic disorders and 3 of whom had bipolar disorder (manic-depressive illness), manifested psychosis, intermittent hyponatremia, and polydipsia (PIP syndrome). The relationship between serum sodium and urinary water excretion among the 10 PIP patients is described in detail. The success of lithium in improving serum sodium levels and in decreasing urinary water excretion among the three PIP patients with bipolar disorder and the failure of changes in urinary water excretion to explain changes in serum sodium levels among the 10 PIP patients argue against "psychogenesis" as the explanation for the polydipsia and excessive water intake as the sole explanation for hyponatremia or complications ascribed to water intoxication.

Adult↗
PubMed1985

Hemodynamic effects of enalapril on neonatal chronic partial ureteral obstruction.

To evaluate the role of angiotensin II (ANG II) in renal vasoconstriction due to ipsilateral CPUO, guinea pigs were subjected to incomplete left ureteral stenosis within the first 48 hr of life, and were given enalapril from the 14th day of life until study at 23 +/- 3 days or 8 weeks of age. Renal blood flow (RBF) was measured using radioactive microspheres, and glomerular filtration rate (GFR) was derived from inulin extraction. The number of perfused glomeruli per kidney was determined following in vivo India ink perfusion. Enalapril treatment resulted in an 83% rise in RBF of the obstructed kidney, from 2.58 +/- 0.26 to 4.73 +/- 0.48 ml/min (P less than 0.001), which was associated with a 26% increase in number of perfused glomeruli (P less than 0.01). Mean GFR of the hydronephrotic kidney increased from 0.13 +/- 0.02 to 0.37 +/- 0.10 ml/min (P less than 0.05). Enalapril had no effect on intraureteral pressure of the obstructed left kidney after 7 to 13 days of administration, and did not affect renal mass or ureteral diameter after 6 weeks of treatment. It is concluded that hemodynamic consequences of CPUO in the neonate may be attenuated by ANG converting enzyme inhibition. The primary effect of enalapril is most likely inhibition of intrarenal ANG II formation.

Angiotensin II↗
PubMed1985

Polymorphonuclear leukocyte: arachidonate edema.

Polymorphonuclear leukocytes (PMN) are important participants in many models of acute lung edema. Enhanced metabolism of arachidonate is also characteristic of many of these models. We found that PMN and arachidonate, but neither alone, increased alveolar capillary permeability of isolated perfused lungs and increased transfer of albumin across monolayers of endothelial cells cultured on micropore filters. Inhibition of PMN, but not endothelial cyclooxygenase, blunted the edematous process. Neither PMN proteases nor PMN-derived oxidants were involved. The edemagenic activity was not found in supernatants of PMN and arachidonate, and unstable prostaglandins did not alter endothelial albumin transfer. The edemagenic process was not inhibited by blocking leukotriene synthesis, and endothelial albumin transfer was not increased by direct addition of leukotrienes to endothelium. These data demonstrate that PMN and arachidonate can interact to increase endothelial permeability and that PMN cyclooxygenase activity is important for this process. This interaction is of potential significance to the acute inflammatory process in the lung vasculature.

Animals↗
PubMed1985

Direct effects of adrenocorticotropic hormone on bovine adrenomedullary cells: adenosine 3',5'-monophosphate-dependent phosphorylation of tyrosine hydroxylase.

Release of adrenal catecholamine by carbachol has been shown to be coincident with an increase in intracellular cAMP levels. Bovine adrenal medullary (BAM) cells were prepared and maintained in culture and used to examine the role of cAMP in stimulus-secretion coupling. The addition of ACTH to these cells caused a 10- to 50-fold increase in cellular cAMP without an effect on catecholamine secretion, suggesting cortical cell contamination. Percoll density separation of both BAM cells and adrenal cortical cells revealed that the greatest cAMP responses to ACTH corresponded to the catecholamine-containing cell fractions and not to those density layers where cortical cells sedimented. BAM cells isolated on Percoll did not metabolize [14C]cholesterol to steroids as would be expected were the ACTH-stimulated cAMP accumulations due to cortical cell contamination of the cultures. ACTH stimulated protein phosphorylation in 32P-labeled BAM cells in a manner indistinguishable from that induced by carbachol and forskolin. The major soluble phosphoprotein to be affected by these agents had a relative mol wt of 55-57 kdaltons on sodium dodecyl sulfate-gels and corresponded to tyrosine hydroxylase, which is a specific marker enzyme in the adrenal for chromaffin cells. We propose that bovine adrenal chromaffin cells express ACTH receptors which are coupled to adenylate cyclase. While no acute effect of ACTH was found on catecholamine secretion, ACTH may play a direct role in the regulation of catecholamine synthesis by stimulating the phosphorylation of tyrosine hydroxylase by cAMP-dependent protein kinase.

Adrenal Medulla↗
PubMed1985

Escape from the sodium-retaining action of intrarenal angiotensins II and III in the conscious dog.

The maximum amounts of angiotensins II and III that were confined to the kidney during intrarenal arterial administration in conscious dogs were determined to be 2 and 12 pmol/kg X min, respectively. These doses were infused chronically intrarenally to uninephrectomized dogs. A significant reduction in urinary volume and excretion of sodium was observed at 24 h of the intrarenal peptide infusions. These excretory effects were more marked with angiotensin III than with angiotensin II. Escape from the antidiuretic and antinatriuretic effects of angiotensins II and III was observed after 24 h in spite of continuous administration of the peptides. To define the role of reduced intrarenal angiotensin concentration in the physiological phenomenon of escape from the sodium-retaining action of mineralocorticoids, angiotensin II or III at the above doses was administered intrarenally together with 11-deoxycorticosterone acetate. No delay in escape from the sodium-retaining effects of the mineralocorticoid was noted as a result of concurrent intrarenal angiotensin administration. In conclusion, both angiotensin II and angiotensin III have direct sodium- and volume-retaining effects on the kidney. These renal effects are abolished within 48 h, either due to tachyphylaxis to angiotensins or by other mechanisms overriding the actions of angiotensins. No association was demonstrated between suppression of the renin-angiotensin system and escape from mineralocorticoid-induced sodium retention.

Aldosterone↗
PubMed1984

Angiotensin III-induced modulation of neurogenic responses in the rabbit vas deferens and portal vein.

The effects of prostaglandin synthesis inhibitors on the presynaptic actions of angiotensin (ang) II and III were examined in isolated rabbit vasa deferentia and portal veins. Ang II caused dose-dependent potentiation of low frequency, nerve stimulation in vasa deferentia and portal vein. Indomethacin (26 microM) enhanced the electrically-induced contractions in the vasa deferentia only but did not alter the potency of ang II in either preparation. In contrast, ang III decreased contractions in vasa deferentia induced by nerve stimulation by up to 36% (10(-6) M) and potentiated these contractions at concentrations higher than 10(-6) M. The inhibitory action of ang III on vasa deferentia was converted to potentiation by pretreatment with indomethacin or mepacrine. Exogenous PGE2 blocked low frequency nerve stimulation and not responses to norepinephrine. This prostaglandin appeared to mimic ang III in the vas deferens. No effects of ang III were observed if the contractions were induced by exogenous alpha adrenergic agonists. [Sar1, Ala8] ang II antagonized all responses to the angiotensins, whereas [Sar1, Cys-CH3(8)] ang II selectively antagonized the angiotensin-induced potentiation. Responses in field-stimulated portal veins were potentiated by ang III and this response was unaffected by indomethacin. This investigation strongly suggests the existence of at least two ang receptors in the vas deferens and demonstrates for the first time selective responses to the octa- and heptapeptides in the same effector organ.

Angiotensin II↗
PubMed1984

Workplace protection factor measurements on powered air-purifying respirators at a secondary lead smelter--test protocol.

A study was conducted at a secondary smelter to evaluate the workplace performance of the 3M Model W-344 and Racal Model AH3 powered air-purifying respirators ( PAPR ) equipped with helmets and high efficiency filters. The research protocol developed for obtaining leakage measurements in the field provides for proper respirator fitting, use, wear, maintenance and worker supervision, all of which are problems commonly associated with data acquisition when field testing respirators. The protocol proved to be very workable, even though it required extensive worker and equipment monitoring. Based upon the successful implementation of this protocol, the performance of these PAPRs should be indicative of their best performance under the workplace conditions experienced in this study. This research protocol is proposed as a model for conducting field studies on other types of respirators as well as the basis on which to develop new and improved field test procedures. The results of one such study are presented in a comparison paper.

Air Pollutants, Occupational↗
PubMed1984

Workplace protection factor measurements on powered air-purifying respirators at a secondary lead smelter: results and discussion.

A study was conducted at a secondary lead smelter to evaluate the workplace performance of the 3M W-344 and Racal AH3 powered air-purifying respirators equipped with helmets and high efficiency filters. The research protocol developed for the study has been described in a companion paper. The results of the study indicate that the mean lead concentrations, measured inside the facepiece of both PAPRs, were significantly less than the OSHA lead exposure limit of 50 micrograms/m3. The means of the workplace protection factor measurements on both PAPRs were significantly less than the PAPR selection guide protection factor classification of 1000. Correlation analysis of preshift quantitative fit factors and corresponding workplace protection factors indicated no linear association between these two measures of performance. This finding suggests that for PAPRs equipped with helmets and high efficiency filters quantitative fit factors as presently determined are not indicative of the workplace protection which the respirators provide. Since the PAPR protection factor classification of 1000 was originally based on quantitative fit factors, the lack of a demonstrated association between quantitative fit factors and workplace protection as found in this study may explain why their performance was significantly less than expected.

Air Pollutants, Occupational↗
PubMed1984

Effects of cytochrome P-450 inhibitors on endothelium-dependent relaxation in rabbit aorta.

Endothelium-dependent relaxation in rabbit aorta was inhibited by exposure to two cytochrome P-450 inhibitors, metyrapone and SKF-525A. Aortic rings were contracted to a stable plateau by addition of phenylephrine (10(-7) M). Relaxation was elicited by the cumulative addition of methacholine (3 X 10(-8) - 3 X 10(-6) M) or A23187 (10(-8) - 10(-6) M). Exposure to metyrapone (500 microM) or SKF-525A (10 micrograms/ml) was found to inhibit relaxation in response to concentrations of methacholine exceeding 10(-7) M. Maximal relaxation was inhibited 73% by metyrapone. Relaxation stimulated by concentrations of A23187 exceeding 10(-7) M was also found to be inhibited by both metyrapone and SKF-525A exposure. Maximum A23187-induced relaxation (55% of the phenylephrine contractile response) was inhibited 40% by metyrapone and 55% by SKF-525A. Arachidonic acid (10-100 microM) also elicited endothelium-dependent relaxation in rings pretreated with indomethacin (10 micrograms/ml) and contracted with phenylephrine. This relaxation response was abolished by exposure to metyrapone or SKF-525A. These results suggest that cytochrome P-450 may be involved in endothelium-dependent relaxation responses, perhaps by metabolizing arachidonic acid to active products.

Animals↗
PubMed1984

Identification and characterization of the rabbit angiotensin II myocardial receptor.

The octapeptide, angiotensin II, elicits a positive inotropic response in myocardial tissue by activating slow calcium channels. Pharmacological studies suggest that the inotropic action of angiotensin II is receptor mediated. The current investigation was performed to characterize the binding of 125I-angiotensin II to the putative receptor in a plasma membrane-sarcoplasmic reticulum preparation of the rabbit left ventricle. In experiments performed at 18 degrees C, steady state binding occurred at 45 minutes and saturable binding was 80-85% of the total binding. Analysis of the binding data indicated that the 125I-angiotensin II interacted with a single class of sites with a Kd = 4.5 +/- 0.8 nM and exhibited a binding capacity of 53.5 +/- 8 fmol/mg protein. The potency order for the competitive binding of analogues and antagonists of angiotensin II paralleled that observed for in vitro contractile force development in bioassay systems utilizing left atrial tissue. The binding of 125I-angiotensin II was stimulated 2-fold in the presence of the divalent cations of calcium and magnesium (10 mM). Guanine nucleotides modified the binding of 125I-angiotensin II to the rabbit myocardial particulate fraction. Guanine triphosphate and nonhydrolyzable analogues of guanine triphosphate increased the dissociation rate of the bound 125I-angiotensin II and decreased hormone binding to the receptor at equilibrium. In the absence of magnesium, guanine nucleotides had no effect on the dissociation rate of 125I-angiotensin II. 125I-Angiotensin II binding to a rabbit myocardial particulate fraction was found to have high affinity, to be saturable, reversible, specific, and modulated by guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗