Cardiac hypertrophy. Mechanical, neural, and endocrine dependence.
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Angiotensin II↗
Biomedical subjects
K M Baker
Publications and source records attributed to K M Baker.
A randomised, double-blind clinical trial of a maltodextrin containing oral rehydration solution in acute infantile diarrhoea.
We compared the efficacy of a maltodextrin containing oral rehydration salts (ORS) solution with that of the WHO recommended glucose-ORS solution in a double blind randomized study of treating 69 children (33 in experimental group; 36 in control group) aged 4-36 months with acute diarrhoea causing mild to moderate dehydration. Both the groups of children were similar in initial clinical characteristics and received only ORS solutions. No significant differences in stool output (median 88.0, range 34-320 g/kg body wt. in experiment vs 75.0, 25-410 g/kg in control), intake of ORS solution (125.0, 58-360 ml/kg body wt. vs 154, 130-250 ml/kg), and duration of recovery from diarrhoea (2.0 d, range 1-6 vs 2.0 d, 1-9) were found between the groups. The haematocrit and serum electrolyte values in the two groups 24 hours after starting treatment were also similar. The results suggest that the ORS containing maltodextrin (50 g/l) in place of glucose has no advantage over WHO-ORS in correcting mild to moderate dehydration of children with acute diarrhoea.
Child, Preschool↗
[Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells.
Cardiac hypertrophy is a process that occurs in response to various mechanical or hormonal stimuli. Stimulation of the renin-angiotensin system is involved in the process of cardiac hypertrophy through mechanisms related to increased peripheral vascular resistance and increased cardiac afterload. In this study we determined whether [Sar1]angiotensin II (ANG II) directly stimulated protein synthesis and cell growth in embryonic chick myocytes in cell culture. Eighteen-day-old embryonic chick myocytes in subconfluent cell culture, incubated in a chemically defined serum-free media, showed a significant increase in total protein content, 18.5, 26.2, and 22.2%, respectively, when exposed to [Sar1]ANG II (1 microM/day) for 5, 7, and 9 days, respectively. The increase in total protein resulted in part from an increase in the fractional protein synthesis rate of 21.7, 16.5, and 14.9% at 5, 7, and 9 days, respectively. Total DNA and RNA levels did not change significantly following a 4-day exposure to [Sar1]ANG II in subconfluent culture. The relative rate of protein synthesis, determined by pulse labeling for 3 h with [3H]phenylalanine, showed increases of 23.4, 22.9, and 17.8% over control after 4, 5, and 6 days of exposure to [Sar1]ANG II. The incorporation of [3H]phenylalanine was blocked by the specific ANG II-receptor antagonist [Sar1,Ile8]ANG II. The data demonstrate a receptor-mediated increase in the rate of protein synthesis in cultured chick myocytes in response to [Sar1]ANG II, with a resultant increase in total cellular protein. This angiotensin peptide appears to directly stimulate protein synthesis in cultured embryonic chick myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats.
We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-Converting Enzyme Inhibitors↗
Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells.
The octapeptide [Ile5]angiotensin II (ANG II), which is the principal circulating hormone of the renin-angiotensin system, could modulate or mediate cardiac hypertrophy via indirect effects, through increases in total peripheral vascular resistance, or by direct effects on cardiac cells, which result in increased protein synthesis and cell growth. In this study we determined whether ANG II stimulated protein synthesis and cell growth in cultures of embryonic chick myocytes. After 3 h of exposure to ANG II, there were significant increases in total cellular protein at 120, 144, and 168 h and in the relative rate of protein synthesis at 120 and 144 h. There was a significant increase in the fractional rate of protein synthesis of 32.2% (0.0119 +/- 0.0008 h-1 for ANG II stimulated and 0.0090 +/- 0.0003 h-1 for control). The stimulatory effects of ANG II on protein synthesis and cell growth were inhibited by the ANG II antagonist [Sar1,Ile8]ANG II and the hexapeptide ANG II-(3-8). ANG II significantly increased total RNA levels in myocytes, at 12 h after exposure to the peptide. The stimulatory effect of ANG II (32%) on total cellular protein was slightly greater than that seen with norepinephrine (20%) in contrast to the greater stimulatory effect seen with phorbol 12,13-dibutyrate (47%). ANG II and [Sar1,Ile8]ANG II each stimulated increases in cytosolic-free Ca2+, whereas ANG II-(3-8) did not. Growth-related effects of changes in the chronotropic state of the myocytes were excluded, in that, ANG II-stimulated increases in protein synthesis and cellular protein were not inhibited by potassium chloride depolarization of the cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Fetal expression of renin, angiotensinogen, and atriopeptin genes in chick heart.
The renin-angiotensin and atriopeptin systems play important roles in the regulation of volume and fluid homeostasis. The two systems have opposing physiologic actions in a number of tissues. Experiments were performed to determine whether there were differences in the developmental expression of the genes for renin, angiotensinogen, and atriopeptin. Using RNA dot blot analysis, we compared levels of gene activity for renin, angiotensinogen, and atriopeptin in right atria, left atria, right ventricle, and left ventricle, from 18-day in ovum and 10-day old White Leghorn chicks. In 18-day embryonic chick heart there was expression of atriopeptin mRNA predominantly in the left and right ventricles. At this age, atriopeptin message was expressed in all four cardiac chambers, left ventricle greater than right ventricle greater than right atria greater than left atria. Renin and angiotensinogen mRNA was expressed in all cardiac chambers with reduced expression in left atria. In 10-day old chicks, renin, angiotensinogen, and atriopeptin mRNA was expressed in atrial tissue with right atria greater than left atria, with no detectable expression in left ventricle, right ventricle, or skeletal muscle. Beta actin was expressed in all four cardiac chambers and skeletal muscle, and was used to normalize signals. Cardiac expression of the genes for renin and angiotensinogen during embryogenesis suggests that the renin-angiotensin system may be involved in the growth and development of the myocardium.
Angiotensinogen↗
Characterization of avian angiotensin II cardiac receptors: coupling to mechanical activity and phosphoinositide metabolism.
We have characterized the avian angiotensin II (AII) cardiac receptor and provide data that this receptor couples to both mechanical activity and phospholipid metabolism in the avian heart. In 10-day-old chicks, 125I-AII bound to a high affinity site (Kd = 10 nmol) and a low affinity site (Kd = 79.4 nmol) with estimated binding capacities of 531 and 1330 fmol/mg protein, respectively. The 125I-AII binding was rapid, saturable, reversible and modulated by divalent cations and guanine nucleotides. The potency order for the competitive binding of angiotensin I and II paralleled that observed for in vitro contractile force development in bioassays utilizing left atrial tissue. In avian heart, AII also produced a dose-dependent accumulation of inositol-1-phosphate which was inhibited by the angiotensin antagonist [Sar1, Ile8]AII. The data demonstrate specific avian AII cardiac receptors and provide the first evidence that these receptors couple to both mechanical activity and phosphoinositide metabolism in avian heart.
Animals↗
Angiotensin II receptor-mediated stimulation of cytosolic-free calcium and inositol phosphates in chick myocytes.
We have described previously positive inotropy and increased levels of inositol-l-phosphate as in vitro responses to angiotensin II in cardiac tissue. In this study, changes in cardiac myocyte-free cytosolic calcium stimulated by angiotensin II were monitored with the fluorescent calcium indicator dye Fura-2. There was an initial peak transient increase followed by a sustained increase in cytosolic-free calcium in response to angiotensin II (10(-9)-10(-6) M). The peak transient response in cytosolic-free calcium after addition of angiotensin II (10(-7) M) occurred at 23 +/- 4 sec and was stimulated 2.16-fold (332 +/- 56 nM) above basal levels (154 +/- 14.7 nM). The calcium response was blocked or reversed by addition of verapamil (10(-8) M), lanthanum (0.2 mM) and zero calcium buffer. Angiotensin II receptor-mediated stimulation of inositol phosphates was quantified after separation by high-performance liquid chromatography in cultured chick heart cells prelabeled with L-myo-[1,2-3H(N)]inositol. A time course indicated that the peak response of the angiotensin II (10(-8) M)-stimulated increase in inositol-1,4,5-trisphosphate was at 30 sec. Angiotensin II (10(-8) M) significantly stimulated inositol-1,4-diphosphate (45%) and inositol-1,4,5-trisphosphate (78%) above basal levels. Bordetella pertussis toxin treatment of myocyte cultures in doses (500 ng/ml, 24 hr) shown to fully ADP-ribosylate a toxin-sensitive 41 KD alpha-subunit, blocked completely the angiotensin II-stimulated increases in inositol 1,4-diphosphate, inositol-1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. The rise in cytosolic-free calcium in response to angiotensin II was not blocked or inhibited by toxin pretreatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin II↗
Identification and characterization of guinea pig angiotensin II ventricular and atrial receptors: coupling to inositol phosphate production.
Angiotensin II elicits a receptor-mediated positive inotropic response in cardiac tissue from most mammalian species by activating voltage-sensitive slow Ca2+ channels. In the guinea pig, we confirm there is no in vitro contractile force development in bioassay systems using isolated hearts or left atrial tissue in response to angiotensin peptides. However, 125I-angiotensin II binding sites that have the characteristics of a membrane receptor were identified in ventricular (myocardial) and atrial membrane preparations from guinea pigs. In ventricles, saturation-binding data yielded an optimal fit to a two-site model with a high-affinity site Kd1 = 3.6 +/- 0.7 nM and a low-affinity site Kd2 = 433 +/- 126 nM and binding capacities of 66 +/- 10 and 821 +/- 49 fmol/mg protein, respectively. In atria, saturation binding data yielded an optimal fit to a two-site model with a high-affinity site Kd1 = 1.6 nM and a low-affinity site Kd2 = 300 nM and capacities of 145 and 752 fmol/mg protein, respectively. The ventricular binding of 125I-angiotensin II was stimulated approximately twofold in the presence of the divalent cations calcium and magnesium (10 mM). Nonhydrolyzable analogues of guanosine triphosphate increased the dissociation rate of the bound 125I-angiotensin II and decreased hormone binding to the receptor at equilibrium. Competition for 125I-angiotensin II binding by an agonist-antagonist analogue series correlated with previous studies obtained in the rabbit, a mammal in which inotropic responses to angiotensin II were demonstrated. The data indicate the presence of angiotensin II myocardial and atrial receptors and a G-type coupling protein in guinea pig. Although this species lacks an inotropic response to angiotensin peptides, there is a dose-dependent increase in inositol-1-phosphate production in response to angiotensin II, and this response is blocked by the selective angiotensin II antagonist [Sar1,Ile8]angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Calcium dependence of phorbol 12,13-dibutyrate-induced force and myosin light chain phosphorylation in arterial smooth muscle.
Phorbol dibutyrate (PDB) is an activator of protein kinase C and has been observed to cause a slow developing contraction in vascular smooth muscle. The mechanism of phorbol ester-induced contraction is unknown. We studied the Ca++-dependence of, and the degree of myosin light chain phosphorylation (MLC-P), during PDB-induced contractions in rabbit aortic rings. PDB elicited concentration-dependent contractions (3 X 10(-8) to 10(-6) M) in rabbit aortic rings incubated in normal (1.6 mM Ca++) physiologic salt solution (PSS). Addition of the Ca++-channel blocker nifedipine (0.1 microM) to PSS or removal or Ca++ from PSS significantly reduced the contractile responses to PDB. Depletion of Ca++ by repeated washes in O Ca++-PSS containing 10(-3) M ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid reduced, but did not eliminate, the responses to PDB. In PSS, PDB significantly increased the fraction of phosphorylated MLC/total MLC to 0.33 from a resting value of 0.20. Ca++ depletion reduced the resting fraction (MLC-P/MLC) to 0.14. PDB-stimulated contractions in Ca++-depleted tissues occurred in the absence of significant increases in MLC-P. Sodium nitroprusside partially relaxed PDB-induced contractions by approximately 50% whether elicited in the presence of 1.6 mM Ca++ or after Ca++ depletion. In both cases relaxation occurred in the absence of statistically significant decreases in MLC phosphorylation. Ca++-dependent MLC phosphorylation may account for a component of the PDB contractile response in rabbit aorta. Studies in the absence of Ca++ suggest that PDB may activate contraction without concomitant MLC-P.
Animals↗
Cardiac and vascular actions of decapeptide angiotensin analogs.
We have reported previously the characterization of the angiotensin (A) II myocardial receptor and provided biological evidence that the inotropic activities of the octapeptide AII are receptor mediated. In addition to the inotropic activities that this compound demonstrates, it also has potent vascular contractile activities. The decapeptide AI exhibits both cardiac (+)-inotropic and vascular contractile activities. The responses to AI are in large part secondary to conversion to smaller peptides, principally the octapeptide AII. To attempt to separate the inotropic and vascular response to these peptides, several decapeptide A analogs with amino acid substitutions in either the 1, 5 or 7 positions were studied. The compounds were as follows: [Sar1Ile5Ala7]AI; [Sar1Ile5 alpha-MeAla7]AI; [Sar1Val5N-MeAla7]AI and [Sar1Val5Sar7]AI. These analogs were studied in rabbit point-stimulated left atria, isometrically contracting aortic rings and competition for [125I]AII binding to myocardial ventricular membranes. All the peptides exhibited partial AII agonist activities in cardiac and vascular tissues with potencies equivalent to or less than AI. The inotropic and vascular contractile response to the decapeptides was decreased in the presence of the A converting enzyme inhibitor enalaprilat. The inotropic and vascular activities of these compounds in the presence of A converting enzyme inhibitor suggest that A converting enzyme may be responsible for the conversion to smaller peptides. Biologically active compounds were obtained with amino acid substitutions in the no. 1, 5 and 7 positions. Sarcosine substitution in position 1 did not enhance vascular potency as was observed with AII analogs.
Angiotensin I↗
Enalapril maleate versus captopril. A comparison of the hormonal and antihypertensive effects.
24 hypertensive patients were randomised into 2 groups to compare the antihypertensive effects of enalapril and captopril over a 10-week period. In the hydrochlorothiazide run-in period, blood pressure was reduced from 171 +/- 4/109 +/- 1mm Hg to 160 +/- 4/103 +/- 1mm Hg (p less than 0.05). Angiotensin-converting enzyme (ACE) inhibition decreased blood pressure to 132 +/- 3/87 +/- 2mm Hg. Captopril decreased diastolic blood pressure significantly more after 3 hours than enalapril (-24 versus -17mm Hg, p less than 0.05). After 10 weeks of therapy, this antihypertensive response was maintained at 134 +/- 3/83 +/- 1mm Hg. There was no difference between the captopril and enalapril treated groups. Acute and chronic responses of plasma renin activity, plasma aldosterone and ACE were determined. There was an acute positive correlation between the rise in plasma renin activity and the fall in blood pressures with captopril but not with enalapril. With chronic treatment there was no difference in the ability of either of the 2 drugs to reduce blood pressure, inhibit ACE, reduce aldosterone or stimulate plasma renin activity.
Adult↗
Captopril versus enalapril maleate: a comparison of antihypertensive and hormonal effects.
The antihypertensive effects of captopril and enalapril maleate were studied over a 10-week period in 24 hypertensive patients randomized into captopril or enalapril treatment groups. Prestudy blood pressure was 171 +/- 4/109 +/- 1 mm Hg and after 4 weeks of hydrochlorothiazide 160 +/- 4/103 +/- 1 (p less than 0.05). With the addition of converting enzyme inhibitor to hydrochlorothiazide the blood pressure decreased at 3 h to 132 +/- 3/87 +/- 2 in the subjects. The diastolic blood pressure decreased acutely more with captopril (-24) than with enalapril (-17) (p less than 0.05). After 10 weeks of combined therapy the depressor response was maintained (134 +/- 3/83 +/- 1) and there was no difference between the diastolic blood pressure in the two groups treated with captopril and enalapril. Acute and chronic responses of plasma renin activity, plasma aldosterone, and converting enzyme to the angiotensin-converting enzyme inhibitor were determined. There was a significant correlation between the acute fall in diastolic blood pressure and rise in plasma renin activity in patients treated with captopril but not with enalapril. In conclusion, there is an acute depressor response with converting enzyme inhibition which is more pronounced with captopril than with enalapril and which correlates with an increase in plasma renin activity. With more prolonged treatment, the two drugs show equivalent efficacy in reducing blood pressure, inhibiting angiotensin-converting enzyme, reducing aldosterone, and stimulating plasma renin activity.
Adult↗
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↗
Left ventricular mural thrombus in a patient with thrombocytosis and agnogenic myeloid metaplasia.
The two factors responsible for the development of left ventricular mural thrombi are endocardial injury secondary to old or recent anterior myocardial infarction and left ventricular dysfunction. Endothelial damage also is thought to be the initial event in the development of arterial thrombi. However, arterial thrombi may develop in patients with thrombocytosis secondary to myeloproliferative disorders in the absence of endothelial injury. A patient had thrombocytosis secondary to agnogenic myeloid metaplasia and a left ventricular mural thrombus developed in the absence of clinical or laboratory evidence of old or coronary angiogram and left ventricular function. To our knowledge, this is the first such case reported.
Aged↗
Antihypertensive effects of angiotensin blockade: saralasin versus captopril.
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Adult↗
Tetrahydropapaveroline: formation in vivo and in vitro in rat brain.
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Adsorption↗
Metabolism of 1-methyl-5-nitro-2-(2'-pyrimidyl)imidazole.
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Acetamides↗