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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac hypertrophy is an adaptive response to an increased load imposed on the myocyte which allows the heart to perform increased work while maintaining normal myocardial fiber stress and shortening in systole. A deleterious consequence of pressure-overload hypertrophy is the prolongation of Ca(2+)-sensitive force inactivation (impaired myocardial relaxation) which is related to intrinsic alterations in cytosolic Ca2+ transport and reuptake in diastole. Additional factors appear to adversely modify myocardial relaxation in the hypertrophied heart, including the imposition of ischemia. There is also evidence that the expression and activity of the cardiac tissue renin angiotensin system (RAS) may be modified in the hypertrophied heart and contribute to diastolic dysfunction. Recent studies have demonstrated the presence of increased cardiac angiotensin converting enzyme (ACE) mRNA expression and activity in animal models of hypertrophy, including the aortic-banded rat with compensatory pressure-overload hypertrophy and rats with post-infarction remodeling. In the beating, isovolumic aortic-banded rat heart, the increased intracardiac activation of angiotensin I to II has been shown to be associated with a dose-dependent depression of diastolic relaxation. Preliminary studies suggest that the depression of diastolic function by angiotensin II in the hypertrophied heart can be prevented by the specific inhibition of cardiac ACE. In addition, the well-recognized susceptibility of the hypertrophied heart to severe ischemic diastolic dysfunction also appears to be favorably modified by the inhibition of cardiac ACE activity. The mechanisms responsible for the adverse effects of angiotensin II on diastolic relaxation in the hypertrophied heart are likely to be complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts. 133 63

The effects of torasemide (0.1 and 1 mg kg-1, i.v.) and furosemide (3 mg kg-1) on renal haemodynamics and excretory responses in the presence of angiotensin II and endothelin-1 was examined in anaesthetized dogs. Angiotensin II or endothelin-1 was continuously infused into the renal artery throughout the experiment and a bolus of torasemide or furosemide was injected into the bracheal vein. Continuous intrarenal arterial (i.r.a.) infusion of angiotensin II, at a dose of 5 ng kg-1 min-1, increased renal vascular resistance (RVR) and decreased renal blood flow (RBF) and glomerular filtration rate (GFR), but had no effect on systemic mean arterial pressure (MAP). Urinary excretion of sodium (UNaV) and urine flow (UF) were significantly decreased during angiotensin II infusion. Intravenous injections of torasemide in the presence of angiotensin II caused a dose-dependent increase in UF, UNaV and urinary excretion of potassium (UKV), while a decrease in RVR was accompanied by an increase in RBF. UKV was greater in the furosemide group than in the torasemide group, despite both groups having the same degree of aquaresis and natriuresis. Continuous i.r.a. infusion of endothelin-1, 1.5 ng kg-1 min-1, produced effects similar to those of angiotensin II on renal haemodynamics; however, the onset of action was extremely slow compared with the effects produced by angiotensin II. Endothelin-1 caused a significant decrease in UF, UNaV and UKV only at a later period, despite a relatively early depression of renal haemodynamics. Torasemide and furosemide also produced a sufficient diuretic action in this model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diuretic action of the novel loop diuretic torasemide in the presence of angiotensin II or endothelin-1 in anaesthetized dogs. 135 Jun 26

Calcium antagonists retard the development of atherosclerosis in cholesterol-fed rabbits and modestly enhance regression after their return to a normal diet. Proliferative lesions following endothelial damage (from, for example, balloon catheter, electrical stimulation) are also diminished. Many mechanisms for these effects have been proposed and their relative importance is not yet clear. However, changes in blood lipid levels do not play an important role. Only a few investigations into how atherosclerosis affects the hemodynamic actions of calcium antagonists have been carried out. Thus, the effects of isradipine were compared in atherosclerotic and normal rabbits. Isradipine increased heart rate and cardiac output less in atherosclerotic rabbits than in normal ones while having no effect on the surface electrocardiogram (ECG). In contrast, the arteriolar vasodilator, dihydralazine, induced ST-segment depression with similar falls in blood pressure, partly explainable by reflex tachycardia and intramyocardial maldistribution of coronary blood flow. Flow to the brain increased with isradipine and decreased with dihydralazine. In atherosclerotic animals, the pressor effects of norepinephrine, phenylephrine, and angiotensin II (Ang II) were amplified. Isradipine partly corrected this enhanced responsiveness. Calcium antagonists thus elicit beneficial hemodynamic and antivasoconstrictor effects in atherosclerotic experimental animals, in addition to having a long-term prophylactic antiatherosclerotic action.
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PMID:Hemodynamic, antivasoconstrictor, and antiatherosclerotic effects of calcium antagonists in animal models of atherosclerosis. 169 7

Angiotensin II inhibits nonadrenergic (purinergic) neurotransmission in the vas deferens and potentiates adrenergic neurotransmission and prostaglandin (PG)E synthesis. Other angiotensin responses are sensitive to either dithiothreitol or pertussis toxin. The present study tested the hypothesis that dithiothreitol or pertussis toxin selectively depress angiotensin responses in the vas deferens. The dithiothreitol (10 mM) eliminated the potentiation of both adrenergic neurotransmission and PGE synthesis but did not alter the depression of purinergic neurotransmission. In contrast, pertussis toxin (100 ng/ml for 3 hr) eliminated the depression of purinergic neurotransmission but had no effect on adrenergic neurotransmission or PGE synthetic responses to angiotensin II. The results are consistent with the existence of at least two transduction pathways for angiotensin II, one enhancing adrenergic neurotransmission and PGE synthesis and the other depressing purinergic neurotransmission. The results indicate that the vas deferens is a useful preparation in defining selective actions of angiotensin receptor agonists or antagonists.
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PMID:Pharmacological differentiation of angiotensin effects in the rabbit isolated vas deferens with dithiothreitol and pertussis toxin. 215 55

We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +/- 1.3%, P less than 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls.
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PMID:Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. 217 12

We examined the effect of two angiotensin receptor antagonists on neuromodulatory and prostaglandin-producing effects of angiotensin II in the rabbit isolated vas deferens because prior studies have established that angiotensins selectively influence the two neural events, one being adrenergic and the other nonadrenergic. Angiotensin II increased adrenergic neurotransmission and prostaglandin E synthesis in a concentration-dependent manner while depressing nonadrenergic neurotransmission. The [1-Sarcosine, 8-Alanine]-angiotensin II preferentially antagonized adrenergic neuromodulatory effects of angiotensin II. In contrast, the nonadrenergic neuromodulatory and prostaglandin E-releasing effects of angiotensin II were suppressed by [1-Sarcosine, 8-Alanine]-angiotensin II to a lesser extent. The nonpeptide angiotensin receptor antagonist, Dupont 753 (2-n-butyl-4-chloro-5-hydroxymethyl-1-[2(1)-(1-H-tetrazol-5-yl) biphenyl-4-yl)methyl] imidazole, potassium salt, exhibited the opposite selectivity. It eliminated the depression of nonadrenergic neurotransmission without significantly altering the potentiation of adrenergic neurotransmission caused by angiotensin II. The angiotensin-induced stimulation of prostaglandin E synthesis was also eliminated by this antagonist. These data suggest that angiotensin effects in the vas deferens are mediated by at least two types of angiotensin receptors.
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PMID:Selective blockade of angiotensin responses in the rabbit isolated vas deferens by angiotensin receptor antagonists. 226 11

Angiotensin II (ANG II) infusion has been reported to impair barrier size selectivity and exacerbate proteinuria in the rat. To examine whether this is also true of humans, we infused a pressor dose of ANG II into seven healthy controls and seven nephrotic patients. A prompt depression of glomerular filtration rate (GFR) and renal plasma flow was observed in each group (P less than 0.01). Surprisingly, the excretion rates of albumin (5.3 +/- 1.6 to 2.8 +/- 0.3 in controls and 4,791 +/- 1,244 to 3,833 +/- 800 micrograms/min in nephrotics) and immunoglobulin G (1.5 +/- 0.4 to 0.8 +/- 0.2 and 305 +/- 87 to 255 +/- 94 micrograms/min, respectively) fell significantly during ANG II infusion. Fractional clearances of dextrans of broad size distribution (radii 34-54 A) were uniformly elevated by ANG II infusion in controls but tended to decline in nephrotics. A heteroporous model of the glomerular capillary wall revealed ANG II to have a negligible effect on membrane-pore structure. However, the depressed GFR lowered the rate at which macromolecule-rich filtrate was formed through a subset of nondiscriminatory pores from 272 to 176 microliters/min in controls and from 394 to 334 microliters/min in nephrotics. We conclude that, in striking contrast to the rat, pressor ANG II infusion has little or no influence on barrier size selectivity in humans but exerts an antiproteinuric effect by lowering the filtered protein load.
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PMID:Effect of angiotensin II infusion on the human glomerular filtration barrier. 247 34

MK-0521 and captopril were orally administered to acute (6 to 8 days after unilateral renal artery constriction) and chronic (2 to 2.5 months after the constriction) 2-kidney Goldblatt hypertensive dogs for 7 to 21 days. MK-0521 lowered the blood pressure to similar extents in the acute and chronic stages of hypertension. The antihypertensive effect of MK-0521 was dose-dependent and persistent even after its cessation. Captopril also produced an antihypertensive effect, although the effect in the chronic stage of hypertension was less prominent than that in the acute stage of hypertension. MK-0521 was more inhibitory on the renin-angiotensin system than captopril. In the acute stage of hypertension, the dogs treated with MK-0521 had increased angiotensin converting enzyme (ACE) activity, while they had decreased plasma angiotensin II level and elevated plasma angiotensin I level and plasma renin activity. These results clarified the inhibitory effect of MK-0521 on ACE. In contrast, in the chronic stage of hypertension, MK-0521 showed no depression of plasma angiotensin II. There were no significant changes in daily urinary volume, and renal clearances of sodium, potassium and creatinine. These results suggest that the major mechanism of the antihypertensive effect of MK-0521 in 2-kidney Goldblatt hypertensive dogs is an inhibition of the ACE. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanisms of maintaining blood pressure between the two stages of 2-kidney Goldblatt hypertensive dogs.
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PMID:[Antihypertensive effect of repeated oral administration of MK-0521 in 2-kidney Goldblatt hypertensive dogs]. 254 80

Angiotensin II stimulates sequential phospholipase C-mediated hydrolysis of initially the polyphosphoinositides and subsequently phosphatidylinositol (PI) in cultured rat aortic smooth muscle cells resulting in biphasic, sustained formation of diacylglycerol (DG). The mechanisms underlying this delayed induction of sustained DG accumulation are unknown but may be related to cellular events including processing of the angiotensin II receptor-ligand complex. In the present study, we characterized the kinetics of angiotensin II receptor sequestration and studied the effects of interventions which interfere with receptor processing on the pattern of angiotensin II-induced DG formation and phosphoinositide hydrolysis. Conversion of the angiotensin II receptor to an acid-resistant form was temperature-dependent, with half-times of 1.5 min at 37 degrees C and 7 min at 19 degrees C. Reducing the temperature to 25 or 19 degrees C caused a marked temporal separation between the two phases of DG accumulation. There was a close temporal correlation between the effect of temperature on receptor sequestration and on sustained DG accumulation. Furthermore, phenylarsine oxide (5 min, 10 microM), which inhibited angiotensin II receptor internalization, also selectively inhibited the sustained phase of DG accumulation (81 +/- 6% inhibition). Monensin and chloroquine, which interfere with receptor processing through the lysosomal-degradative pathway, had no effect on angiotensin II-induced DG formation in these cells, suggesting that the processing event important to hormonally induced sustained DG accumulation occurs early in the internalization pathway, probably at the level of the plasma membrane. Moreover, the acid-resistant state of the angiotensin II receptor-ligand complex retained its ability to signal, since removal of the surface signal by competitive antagonism with Sar1-Ile8-angiotensin II or acid-wash only slowly reversed accumulation of DG and depression of total cell calcium. These experiments support our previous observation that the initial and sustained phases of angiotensin II-induced diacylglycerol formation in vascular smooth muscle are differentially controlled and suggest that an early event in the cellular processing of the angiotensin II-receptor complex is essential to maintenance of DG accumulation.
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PMID:Correlation of receptor sequestration with sustained diacylglycerol accumulation in angiotensin II-stimulated cultured vascular smooth muscle cells. 282 94

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.
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PMID:Alpha adrenergic receptors mediate angiotensin-induced prostaglandin production in the rabbit isolated vas deferens. 302 11


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