UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that in cardiac muscles, angiotensin II partially inhibits the contractile response to beta-agonists. We studied the contractile response of isolated rat left ventricular papillary muscles to isoproterenol and the effect of angiotensin II on this response. We also investigated whether the effect of angiotensin II is mediated by bradykinin, prostaglandins, nitric oxide, and/or cGMP. Contractility of isolated papillary muscles was recorded with a force transducer, and rest tension, maximal developed tension (DT), maximal rate of rise in developed tension [T(+)], and maximal velocity of relaxation [T(-)] were measured (1) under basal conditions, (2) after pretreatment with various drugs, and (3) after cumulative doses of isoproterenol. Pretreatment groups included (1) vehicle (controls); (2) angiotensin II; (3) angiotensin II and N(omega)-nitro-L-arginine, an inhibitor of nitric oxide release; (4) L-arginine, the substrate for nitric oxide synthase; (5) L-arginine and N(omega)-nitro-L-arginine; (6) 8-bromo-cGMP, analogous to the second messenger of nitric oxide; (7) angiotensin II and icatibant (Hoe 140), a bradykinin B2 antagonist; and (8) angiotensin II and indomethacin, a cyclooxygenase inhibitor. There were no differences in contractile parameters before and after any of the pretreatments. Isoproterenol increased DT, T(+), and T(-), and these effects were attenuated by angiotensin II, L-arginine, and 8-bromo-cGMP. The effects of angiotensin II and L-arginine were blocked by inhibition of nitric oxide release with N(omega)-nitro-L-arginine. Neither the bradykinin B2 antagonist nor the cyclooxygenase inhibitor altered the effects of angiotensin II. We concluded that angiotensin II partially inhibits the contractile response of cardiac papillary muscles to isoproterenol This effect is likely mediated by nitric oxide release, perhaps acting via cGMP. Kinins and prostaglandins do not appear to participate in the inhibitory effect of angiotensin II. Attenuation of the contractile effect of isoproterenol by angiotensin II may help explain why cardiac function improves in heart failure after blockade of the renin-angiotensin system.
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PMID:Myocardial contractility is modulated by angiotensin II via nitric oxide. 861 28

Antidromic stimulation of cardiac sensory C fibers releases calcitonin gene-related peptide (CGRP), which increases heart rate, contractility, and coronary flow. C-fiber endings are closely associated with mast cells, and CGRP may release mast-cell histamine. Because prejunctional histamine H3-receptors inhibit transmitter release from autonomic nerves, we tested the hypothesis that H3-receptors modulate CGRP release in the heart. CGRP released by bradykinin in the electrically paced guinea pig left atrium and by capsaicin in the spontaneously beating isolated heart caused marked positive inotropic and chronotropic effects, respectively. Capsaicin significantly enhanced the overflow of CGRP (fivefold) and histamine (twofold) into the coronary effluent. All of these effects were prevented by prior chemical destruction of C fibers in vivo. The H3-receptor agonist imetit attenuated the inotropic response to bradykinin by 50%. Imetit also decreased the capsaicin-induced tachycardia and the increase in CGRP overflow by 50%. Imetit, however, did not modify the response to exogenous CGRP. The effects of imetit were blocked by the H3-receptor antagonist thioperamide. Notably, thioperamide by itself potentiated the capsaicin-evoked increases in heart rate and CGRP overflow (by 25% and 50%, respectively). Thus, our findings identify a negative-feedback loop, whereby CGRP releases histamine from cardiac mast cells and histamine in turn inhibits CGRP releases by activating H3-receptors on C-fiber terminals. Because CGRP release is augmented in pathophysiological conditions, such as septic shock, heart failure, and acute myocardial infarction, modulation of CGRP release may be clinically relevant.
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PMID:Histamine H3-receptor-mediated inhibition of calcitonin gene-related peptide release from cardiac C fibers. A regulatory negative-feedback loop. 862 Jun 7

Left ventricular remodeling is a dynamic process that occurs in reaction to an insult to the myocardium. The response to either loss of cells, as may occur following myocardial infarction, or to hemodynamic overload, as may occur in aortic stenosis, is an attempt to maintain cardiac output and normalize wall tension. This is accomplished through the activation of the renin-angiotensin system and hypertrophy of noninfarcted segments of the myocardium. in the case of moderate or large infarctions these mechanisms fail to normalize wall stress. The stimulus to further remodeling remains, viable myocytes hypertrophy (with greater increases in cell length than width), the mass-to-volume ratio increases, and an exponential increase in wall stress results. This increase in myocyte tension has been associated with premature myocyte cell death. Thus, a vicious cycle is established wherein overstretch of the myocardium while sustaining cardiac output leads to progressive myocyte loss and left ventricular dilation. The renin-angiotensin system plays an integral role in this process. Its inhibition by angiotensin-converting enzyme (ACE) inhibitors both chronically and immediately after myocardial infarction has been shown to decrease left ventricular volumes and reduce mortality. Controversy exists regarding the mechanism through which ACE inhibitors exert their effects. ACE inhibitors reduce afterload/preload, circulating angiotensin II levels, and raise circulating levels of bradykinin. It is not yet clear which mechanism is responsible for the greatest impact on left ventricular dilation and mortality. inhibition of the renin-angiotensin system is clearly beneficial to cardiac performance as well as morbidity and mortality when myocardium is lost and heart failure ensues. Specific modes of action require further definition, including local and systemic effects. Possible benefits of angiotensin receptor blockade versus augmentation of bradykinin requires definition, setting the stage for further study, while the beneficial therapeutic use of these agents continues.
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PMID:The renin-angiotensin system in left ventricular remodeling. 863 27

Heart failure is a physiopathological condition, with an increasing incidence and prevalence, involving the action of a series of mechanisms known as 'compensators', which are phylogenetically ready to normalize minute volume and blood pressure. These mechanisms include the activation of a series of neurohormonal systems: the sympathetic nervous system, the aldosterone renin-angiotensin system, vasopressin arginine, endothelin, which are basically vasoconstrictors, with the counterpoint of other vasodilator systems, such as the endothelial relaxation factor, certain prostaglandins and the bradykinin-kallikrein system, which modulate global response. The authors review the physiopathology of each of these systems, as well as their significance in the diagnosis and prognostic evaluation of heart failure. We analyze the possible deleterious effects of neurohormonal activation, anatomically and at the cardiovascular function level, and try to determine if they are capable of explaining the evolution and progression of heart failure, in a truly vicious circle, up until the irreversible heart failure phase. We review the current importance of the inhibition of the aldosterone renin-angiotensin system in the prophylaxis and treatment of heart failure. Furthermore, we describe the present-day value of the inhibition of the sympathetic nervous system in some forms of heart failure. We also analyze the different pharmacological treatment for heart failure: diuretics, inotropic agents, vasodilators (in their different pharmacological types), paying particular attention to their action on neurohormonal systems and their implications in the prognosis and evolution of heart failure.
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PMID:[Neurohormonal factors in heart failure. I]. 865 Mar 99

Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is unknown. We have investigated the possibility that the inflammatory peptide bradykinin, normally degraded by ACE, causes sensitization of airway sensory nerves and an enhancement of the cough reflex in conscious guinea pigs. Treatment of guinea pigs for two weeks with captopril led to an increased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist icatibant. A similar icatibant-sensitive enhancement of citric acid-evoked cough was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic saline was unaffected. In electrophysiological studies performed in vitro, responses of single vagal C fibers to capsaicin, applied to receptive fields of single-fiber units in the trachea, were also markedly increased after perfusion with bradykinin, whereas A delta fiber responses to hypertonic saline were unaffected. These results indicate that bradykinin-evoked sensitization of airway sensory nerves may underlie the pathogenesis of ACE-inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and other inflammatory conditions.
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PMID:Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough. 867 30

In addition to inhibition of the circulating renin-angiotensin system, specific inhibition of the cardiac effects of angiotensin II (Ang II) represents an important therapeutic goal in the treatment of clinical heart failure. Subtype 1-specific Ang II receptor (AT1) antagonists have been developed to overcome potential limitations of angiotensin converting enzyme inhibitors, e.g. insufficient control of tissue Ang II production and bradykinin-related side effects. Clinical studies have demonstrated beneficial effects of AT1 antagonists. In a single-dose study, the AT1 antagonist losartan decreased the mean arterial pressure and pulmonary arterial pressure while increasing the cardiac index. Effects were dose dependent. Haemodynamic effects were greater with higher doses, but neurohormonal counter-regulation probably also increased, leading to relatively high levels of circulating Ang II with the 150-mg dose, A decrease in plasma levels of noradrenaline, atrial natriuretic factor, and aldosterone reached partial significance. Administration of multiple doses of losartan for 12 weeks also led to favourable haemodynamic and clinical results. Arterial blood pressure, pulmonary capillary wedge pressure, and systemic vascular resistance decreased. The neurohormonal effects of 12 weeks' administration of AT1 antagonists consisted in a decrease in plasma aldosterone concentrations. Whereas AT1 antagonists may counteract the effects of Ang II on the vasculature, and therefore are effective vasodilators, their direct myocardial effects are less clear. The subtype AT2, which represents the dominant, receptor in both healthy and failing human myocardium, is not blocked by AT1 inhibition. Angiotensin receptors on isolated human cardiac fibroblasts stimulate cellular proliferation via a yet undertermined receptor subtype. AT1 antagonists exert beneficial haemodynamic and neurohormonal effects in human heart failure. Their direct myocardial effects require further investigation.
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PMID:Effects of angiotensin receptor antagonists in heart failure: clinical and experimental aspects. 868 68

Heart failure is a physiopathological condition, with an increasing incidence and prevalence, involving the action of a series of mechanisms known as "compensators", which are phylogenetically ready to normalize minute volume and blood pressure. These mechanisms include the activation of a series of neurohormonal systems: the sympathetic nervous system, the aldosterone renin-angiotensin system, vasopressin arginine, endothelin, which are basically vasoconstrictors, with the counterpoint of other vasodilator systems, such as the endothelial relaxation factor, certain prostaglandins and the bradykinin-kallikrein system, which modulate global response. The authors review the physiopathology of each of these systems, as well as their significance in the diagnosis and prognostic evaluation of heart failure. We analyze the possible deleterious effects of neurohormonal activation, anatomically and at the cardiovascular function level, and try to determine if they are capable of explaining the evolution and progression of heart failure, in a truly vicious circle, up until the irreversible heart failure phase. We review the current importance of the inhibition of the aldosterone renin-angiotensin system in the prophylaxis and treatment of heart failure. Furthermore, we describe the present-day value of the inhibition of the sympathetic nervous system in some forms of heart failure. We also analyze the different pharmacological treatments for heart failure: diuretics, inotropic agents, vasodilators (in their different pharmacological types), paying particular attention to their action on neurohormonal systems and their implications in the prognosis and evolution of heart failure.
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PMID:[Neurohormonal factors in heart failure. II]. 874 85

Heart failure is a physiopathological condition, with an increasing incidence and prevalence, involving the action of a series of mechanisms known as "compensators", which are phylogenetically ready to normalize minute volume and blood pressure. These mechanisms include the activation of a series of neurohormonal systems: the sympathetic nervous system, the aldosterone renin-angiotensin system, vasopressin arginine, endothelin, which are basically vasoconstrictors, with the counterpoint of other vasodilator systems, such as the endothelial relaxation factor, certain prostaglandins and the bradykinin-kallikrein system, which modulate global response. The authors review the physiopathology of each of these system, as well as their significance in the diagnosis and prognostic evaluation of heart failure. We analyze the possible deleterious effects of neurohormonal activation, anatomically and at cardiovascular function level, and try to determine if they are capable of explaining the evolution and progression of heart failure, in a truly vicious circle, up until the irreversible heart failure phase. We review the current importance of the inhibition of the aldosterone renin-angiotensin system in the prophylaxis and treatment of heart failure. Furthermore, we describe the present-day value of the inhibition of the sympathetic nervous system in some forms of heart failure. We also analyze the different pharmacological treatments for heart failure: diuretics, inotropic agents, vasodilators (in their different pharmacological types), paying particular attention to their action on neurohormonal systems and their implications in the prognosis and evolution of heart failure.
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PMID:[Neurohormonal factors in heart failure (and III)]. 875 6

To determine the role of the renin-angiotensin system and the bradykinin pathway in the mechanism of action of angiotensin-converting enzyme inhibitors in heart failure, the acute effects of enalaprilat (1 mg/kg) were compared with those of a renin inhibitor (ciprokiren, 1 mg/kg i.v.) in 10 chronically instrumented conscious dogs with heart failure induced by right ventricular pacing (3 wk, 240 beats/min). The effects of enalaprilat and ciprokiren on bradykinin infusion (3, 10, and 30 micrograms/min) and the effects of enalaprilat in the presence of the bradykinin B2 receptor antagonist Hoe-140 (10 micrograms/kg i.v.) were also examined. Both inhibitors significantly decreased mean aortic pressure and increased cardiac output. However, enalaprilat induced significantly greater hemodynamic effects than ciprokiren (mean aortic pressure, -13 +/- 3 vs. -6 +/- 1 mmHg; cardiac output, 0.4 +/- 0.1 vs. 0.15 +/- 0.1 l/min). Bradykinin infusion led to dose-dependent decreases in mean aortic pressure and increases in cardiac output that were not modified by pretreatment with ciprokiren but were potentiated 10-fold by enalaprilat. Hoe-140 significantly reduced the hemodynamic effects of enalaprilat. Thus endogenous bradykinin is involved in the acute hemodynamic effects of enalaprilat in experimental heart failure.
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PMID:Bradykinin pathway is involved in acute hemodynamic effects of enalaprilat in dogs with heart failure. 876 48

Our hypothesis is that regulation of the lung vessel tone and microvascular permeability may be disrupted in chronic heart failure (CHF) and angiotensin converting enzyme (ACE) inhibition may contribute to their readjustment. This hypothesis is based on the fact that KII-ACE, the same enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the luminal surface of the lung vessels and its blockade in CHF may reduce their exposure to an excess of angiotensin II and augment the action of prostaglandins and nitric oxide (NO) deriving from local kinin hyperconcentration. We probed whether ACE-inhibitors influence the pulmonary function; this is peculiar of CHF; they act as KII- or ACE-blockers. Aspirin was utilized as a prostaglandin synthesis inhibitor. We investigated 16 CHF patients and 16 age- and sex-matched normal volunteers or mild untreated hypertensives. All were non-smokers, not taking ACE-inhibitors, aspirin or other cyclooxygenase inhibitors. Pulmonary function tests, exercise testing with respiratory gases and echocardiography were performed in the run-in and repeated at the end of placebo, enalapril (10 mg t.i.d.), enalapril plus aspirin (325 mg/day) and aspirin given in random order and double-blind fashion for 15 days each. Enalapril, as compared to placebo, caused an increase in mean voluntary ventilation (MVV) and alveolar-capillary diffusing capacity for carbon monoxide (DLCO) in CHF, that were counteracted by the addition of aspirin. Aspirin alone was not effective. Enalapril and aspirin were ineffective on the pulmonary function of controls. As to the functional capacity, enalapril increased exercise tolerance time, oxygen consumption (VO2p), minute ventilation (VEp) tidal volume (VTp) and reduced the ratio of volume of dead space gas (VDp) to VTp (VD/VTp), at peak exercise in CHF patients. These effects all were inhibited by the combination of aspirin and were not observed in controls. In CHF VO2p changes from placebo correlated with those in DLCO (r = 0.80, p < 0.0001) and not with those in ejection fraction. This correlation was abolished by aspirin and was not seen in controls. Variations in VD/VTp in CHF patients while on enalapril were related to those in DLCO (r = -0.69, p = 0.003). In CHF the ventilatory equivalent for carbon dioxide production per minute at 1 liter was diminished with enalapril and not in combination with aspirin. Derangements related to CHF are the substrate for benefits of ACE-inhibition on pulmonary function and exercise capacity. Pulmonary diffusion limitation is an important mediator of exercise impairment and its improvement with enalapril goes in parallel with VD/VT, MVV, VT, VE to VCO2 relationship and not with ejection fraction. These patterns reflect changes occurring within the lung that are not related to left ventricular function. The counteracting influence of aspirin on these affects bespeaks a substantial participation of prostaglandins that might readjust capillary permeability and lung interstitial fluid content or alveolar capillary membrane diffusing capacity.
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PMID:[Acetylsalicylic acid antagonism vs ACE inhibitor in congestive heart failure as shown by a diminished respiratory and exercise capacity]. 876 15

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