RESUMEN
Phosphoinositide (PI) turnover, chronotropic and inotropic responses to alpha 1-adrenoceptor activation, and alpha 1-adrenoceptor density were studied in atria from rats with left ventricular myocardial infarction (LVMI) and noninfarcted rats. LVMI was produced after surgical ligation of the left coronary artery in 8-week-old Wistar rats. Rats were killed 4 weeks after this operation when rats with LVMI had developed significant hypertrophy of both ventricles and atria. Phenylephrine 0.1 mM to 1 mM, with propranolol 0.3 mM, produced a concentration-dependent increase in heart rate (HR) in right atria from noninfarcted rat hearts, and this response was significantly reduced in rats with LVMI. In electrically driven left atria, the concentration-dependent, phenylephrine-induced positive inotropic responses observed with propranolol added were also significantly impaired in rats with LVMI as compared with those of noninfarcted rats. In contrast, neither PI turnover in response to phenylephrine in the presence of propranolol nor alpha 1-adrenoceptor density was reduced in rats with LVMI. These results suggest that the impaired alpha 1-adrenoceptor-induced chronotropic and inotropic responses in atria from rats with LVMI are not due to downregulation of alpha 1-adrenoceptors or to impaired activation of PI turnover after alpha 1-adrenoceptor stimulation, but to impairment of one or more biochemical responses distal to PI hydrolysis or changes in coupling mechanisms other than hydrolysis of PIs.
Asunto(s)
Corazón/fisiopatología , Infarto del Miocardio/fisiopatología , Receptores Adrenérgicos alfa/fisiología , Animales , Enfermedad Crónica , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Fosfatos de Inositol/metabolismo , Masculino , Contracción Miocárdica/efectos de los fármacos , Tamaño de los Órganos , Fenilefrina/farmacología , Prazosina/metabolismo , RatasRESUMEN
The long-term effects of perindopril or chlorothiazide therapy were studied in rats after the induction of myocardial infarction by coronary artery ligation. Rats with infarction developed marked cardiomegaly, indicating the presence of chronic left ventricular dysfunction. The ratio of the norepinephrine metabolite, 3,4-dihydroxyphenylethylene glycol (DHPG) to norepinephrine (NE) was elevated in the right ventricle of rats with infarction, suggesting a chronic increase in cardiac sympathetic activity. Perindopril therapy commenced either immediately following infarction or 4 weeks following infarction reduced DHPG/NE ratios toward normal levels, and prevented or reversed cardiac hypertrophy. In contrast, chlorothiazide therapy significantly reduced DHPG/NE ratios but did not decrease cardiac hypertrophy. Perindopril reverses or prevents cardiac hypertrophy and chronic cardiac sympathetic hyperactivity following myocardial infarction, while chlorothiazide reduces cardiac sympathetic activity without influencing cardiomegaly.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Clorotiazida/uso terapéutico , Indoles/uso terapéutico , Infarto del Miocardio/complicaciones , Sistema Nervioso Simpático/efectos de los fármacos , Animales , Cardiomegalia/etiología , Femenino , Metoxihidroxifenilglicol/análogos & derivados , Metoxihidroxifenilglicol/metabolismo , Norepinefrina/metabolismo , Perindopril , Ratas , Ratas EndogámicasRESUMEN
Reduced homeostatic capacity is typical of the aging process and is particularly apparent in changes in the neuroendocrine control of cardiovascular homeostasis. Not only is there reduced beta-adrenoceptor responsiveness, but reduced baroreflex function also occurs with age. These result in increased sensitivity to the therapeutic and postural hypotensive effects of diuretics and vasodilators. Increased total body sodium and reduced activity of the renin-angiotensin-aldosterone system may also contribute to the therapeutic effect of diuretics and salt restriction in elderly hypertensives. In addition, atrial natriuretic peptide levels are increased in the elderly and may in part be responsible for the suppressed renin and aldosterone levels found in older groups. Vasopressin secretion and thirst are also disturbed with age, and may act in concert with declining renal function to predispose the elderly to disturbances of water balance. An understanding of these neuroendocrine changes with age is important to maximize therapeutic benefit and to minimize adverse effects in the treatment of hypertension in the elderly.
Asunto(s)
Envejecimiento/fisiología , Fenómenos Fisiológicos Cardiovasculares , Homeostasis/fisiología , Sistemas Neurosecretores/fisiología , Anciano , Antihipertensivos/efectos adversos , Humanos , Presorreceptores/fisiología , Sistema Nervioso Simpático/fisiología , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
1. The effects of low or high sodium intake for 4 weeks on cardiac catecholamines and 3,4-dihydroxyphenylethylene glycol (DHPG) levels were studied in adult female Wistar rats. 2. Rats receiving the low sodium diet had significantly higher plasma renin activity than rats receiving the high sodium diet. 3. Dopamine concentrations in both the right and left ventricle were significantly higher in the low salt compared with the high salt rats, but noradrenaline, adrenaline and DHPG levels did not differ significantly between the two groups. 4. These data do not support previous reports that sodium restriction reduces cardiac noradrenaline release, but suggest that alterations in sodium intake may influence cardiac noradrenaline metabolism.
Asunto(s)
Catecolaminas/metabolismo , Dieta Hiposódica , Glicoles/metabolismo , Metoxihidroxifenilglicol/metabolismo , Miocardio/metabolismo , Animales , Dopamina/metabolismo , Epinefrina/metabolismo , Femenino , Corazón/efectos de los fármacos , Norepinefrina/metabolismo , Tamaño de los Órganos , Radioinmunoensayo , Ratas , Ratas EndogámicasRESUMEN
The natriuretic, diuretic, and hypotensive effects of atrial natriuretic peptide (ANP) were examined in rats 4 wk after myocardial infarction induced by left coronary artery ligation. Synthetic rat ANP (fragment 1-28) was infused intravenously in doses of 0.1, 0.3, and 1.0 micrograms.kg-1.min-1 for 30 min. There was a significant decrease in systolic blood pressure in controls and rats with infarction, although only in control rats was there a significant decrease in diastolic blood pressure. Changes in systolic and diastolic blood pressure were attenuated in rats with infarction compared with controls (P less than 0.01). The diuretic and natriuretic effects of ANP were observed in both groups of rats, but the effects were significantly less in rats with infarction (P less than 0.01). The ANP infusion did not induce significant changes in heart rate or hematocrit in controls or rats with infarction. The results indicate that rats with chronic left heart failure are less sensitive to the natriuretic, diuretic, and hypotensive effects of ANP when compared with controls. The attenuated renal response to ANP may contribute to the impaired sodium and water excretion in chronic heart failure, although other mechanisms are involved.
Asunto(s)
Factor Natriurético Atrial/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Corazón/fisiopatología , Riñón/fisiopatología , Infarto del Miocardio/fisiopatología , Animales , Femenino , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Potasio/orina , Ratas , Ratas Endogámicas , Valores de Referencia , Sodio/orina , Micción/efectos de los fármacosRESUMEN
Plasma concentrations of immunoreactive atrial natriuretic peptide (mean (SEM] were measured in 135 patients admitted to two coronary care units with myocardial infarction, ischaemic chest pain, or non-ischaemic chest pain. Concentrations were significantly higher in patients with acute myocardial infarction not treated with systemic thrombolysis (60.4 (14.3) pg/ml) than in patients with non-ischaemic chest pain (21.1 (4.3) pg/ml). Patients with ischaemic chest pain had intermediate values (39.3 (7.1) pg/ml). Patients with acute myocardial infarction treated with intravenous streptokinase had normal concentrations of plasma atrial natriuretic peptide (20.2 (3.6) pg/mg), which were significantly lower than those in patients with myocardial infarction not given streptokinase. These changes could not be explained by factors such as age, pre-existing hypertension, renal dysfunction, or cardiac failure, nor treatment other than streptokinase. Raised plasma concentrations of atrial natriuretic peptide in acute myocardial infarction may be a homoeostatic response acting to reduce atrial pressures by natriuresis, diuresis, and venodilatation. The lower concentrations of atrial natriuretic peptide in patients with acute myocardial infarction treated with streptokinase may reflect a short term beneficial haemodynamic effect of streptokinase.
Asunto(s)
Factor Natriurético Atrial/sangre , Infarto del Miocardio/sangre , Estreptoquinasa/uso terapéutico , Angina de Pecho/sangre , Dolor en el Pecho/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
Cardiac norepinephrine (NE), dopamine (DA), epinephrine (Epi), and dihydroxyphenylethylene glycol (DHPG) (a major neuronal metabolite of NE) content were measured in rats with cardiac failure resulting from left ventricular myocardial infarction (LVMI) induced by coronary ligation. The ratio of DHPG/NE was significantly higher in both the right ventricle and interventricular septum of rats with LVMI compared with controls, reflecting a tendency for cardiac DHPG content to rise and NE content to fall during cardiac failure. Cardiac DA and Epi content did not significantly differ between rats with LVMI and controls. Elevated DHPG/NE ratios apparently reflected the increase in NE turnover that accompanies elevated sympathetic activity in heart failure more precisely than changes in NE levels or DHPG levels alone. Furthermore, DHPG/NE ratios are not influenced by increases in cardiac weight due to cardiac hypertrophy. The DHPG/NE ratios may be a useful index of cardiac sympathetic activity for future studies of the effects of drug treatment of cardiac failure in this animal model.
Asunto(s)
Catecolaminas/metabolismo , Glicoles/metabolismo , Insuficiencia Cardíaca/metabolismo , Metoxihidroxifenilglicol/metabolismo , Miocardio/metabolismo , Animales , Vasos Coronarios/fisiología , Modelos Animales de Enfermedad , Femenino , Metoxihidroxifenilglicol/análogos & derivados , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
1. Left ventricular myocardial infarction was induced in female Wistar rats by ligation of the left anterior descending coronary artery. 2. One month following operation, rats with infarcts developed marked cardiomegaly compared to sham operated rats, indicating the presence of chronic left ventricular failure. 3. The ratio of the noradrenaline metabolite 3,4-dihydroxyphenylethylene glycol (DHPG) to noradrenaline (NA) was elevated in the right ventricle of rats with heart failure one month following infarction, suggesting a chronic increase in cardiac sympathetic activity. 4. Perindopril therapy for one month commenced 4 weeks after infarction returned cardiac weights to normal and significantly reduced right ventricular DHPG/NA ratios. 5. The results suggest that ACE inhibition with perindopril reduces elevated levels of cardiac sympathetic activity in rats with chronic left ventricular failure and leads to regression of cardiomegaly.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Catecolaminas/metabolismo , Glicoles/metabolismo , Indoles/uso terapéutico , Metoxihidroxifenilglicol/metabolismo , Infarto del Miocardio/metabolismo , Miocardio/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Enfermedad Crónica , Femenino , Metoxihidroxifenilglicol/análogos & derivados , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , Perindopril , Ratas , Ratas EndogámicasRESUMEN
The natriuretic, diuretic, and hypotensive responses to infused atrial natriuretic peptide (ANP) were measured in rats 4 weeks after myocardial infarction induced by coronary artery ligation. Rat [1-28]-ANP was infused intravenously in doses of 0.1, 0.3, and 1.0 microgram/kg/min for 30 min each under pentobarbital anesthesia. There was a marked natriuresis, diuresis, and fall in blood pressure in rats with infarction but each response was significantly attenuated when compared with sham-operated controls (ANOVA: p less than 0.01, p less than 0.05, and p less than 0.01, respectively). Urinary cyclic guanosine monophosphate (cGMP) excretion in rats with infarction was higher than that of controls but rose to the same absolute level in both groups in response to ANP infusion (0.3 microgram/kg/min). Reduced ANP responsiveness may result from impaired postreceptor mechanisms or from physiological antagonism by angiotensin II. Reduced ANP responsiveness may partly explain impaired salt handling in heart failure.
Asunto(s)
Factor Natriurético Atrial/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Animales , Factor Natriurético Atrial/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Enfermedad Crónica , Vasos Coronarios/fisiología , GMP Cíclico/orina , Femenino , Insuficiencia Cardíaca/fisiopatología , Infarto del Miocardio/fisiopatología , Ratas , Ratas Endogámicas , Sodio/orina , Urodinámica/efectos de los fármacosRESUMEN
Neuropeptide (NPY) and norepinephrine (NE) concentrations were measured in the right ventricle (RV) of rats with cardiac failure resulting from coronary artery ligation. RV NE concentrations fell significantly in rats with infarcts while RV NPY concentrations were unaltered.
Asunto(s)
Gasto Cardíaco Bajo/metabolismo , Neuropéptido Y/metabolismo , Animales , Gasto Cardíaco Bajo/etiología , Vasos Coronarios , Femenino , Ventrículos Cardíacos/inervación , Ventrículos Cardíacos/metabolismo , Infarto/etiología , Infarto/metabolismo , Ligadura , Norepinefrina/metabolismo , Ratas , Ratas Endogámicas , Sistema Nervioso Simpático/metabolismoRESUMEN
The effects of salt restriction and the ACE inhibitor enalapril were compared in a model of chronic myocardial infarction in the rat. Total exchangeable sodium was measured by an isotopic dilution technique to quantitate the effects of the low salt diet and ACE inhibitor on body sodium and extracellular fluid. Rats with infarction developed a marked increase in cardiac weight (4.29 +/- 0.18 mg/g body weight) compared with control rats (3.64 +/- 0.08 mg/g, p less than 0.01). There was hypertrophy of both left and right ventricles. Salt restricted rats with infarction developed identical cardiomegaly (4.30 +/- 0.11 mg/g), although total exchangeable body sodium fell by 10% (p less than 0.001). In contrast, rats with infarction receiving enalapril developed significantly less cardiomegaly (3.97 +/- 0.10 mg/g) while body sodium remained unchanged. Rats with infarction had a significant increase in lung weight which was not changed by salt restriction but which was abolished by enalapril. These results suggest that salt restriction does not prevent the progression of cardiomegaly in chronic left heart failure. In contrast our results confirm the ability of ACE inhibitors to prevent progressive cardiomegaly and left heart failure without affecting long-term changes in sodium balance.
Asunto(s)
Cardiomegalia/prevención & control , Dieta Hiposódica , Enalapril/uso terapéutico , Infarto del Miocardio/prevención & control , Sodio/metabolismo , Animales , Femenino , Infarto del Miocardio/dietoterapia , Infarto del Miocardio/tratamiento farmacológico , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
In chronic cardiac failure, various neurohumoral mechanisms are activated to sustain blood volume, blood pressure, and organ perfusion. Using the coronary artery ligation model of heart failure in the rat, we have measured changes in vasoactive hormone secretion and related these changes to salt and water status during a 1-month period. When compared with controls, rats with infarction had a marked rise in plasma atrial natriuretic peptide (294 +/- 59 vs. 79 +/- 10 pg/ml, p less than 0.001) although there was no increase in total exchangeable body sodium. Plasma renin activity and plasma aldosterone concentrations were the same for both rats with infarction and controls. Similarly, there were no significant differences in plasma arginine vasopressin, plasma osmolality, or plasma sodium concentration in rats with infarction. Ventricular norepinephrine levels were reduced in animals with infarction (p less than 0.01). Plasma atrial natriuretic peptide levels were raised in this model of chronic left ventricular failure. However, there was no salt retention and little stimulation of the renin-angiotensin-aldosterone system or vasopressin. The results suggest that high circulating atrial natriuretic peptide levels may prevent or limit salt and water retention, either directly or indirectly, by inhibiting the renin-angiotensin-aldosterone system.
Asunto(s)
Infarto del Miocardio/metabolismo , Neurotransmisores/metabolismo , Aldosterona/sangre , Animales , Arginina Vasopresina/sangre , Factor Natriurético Atrial/sangre , Catecolaminas/metabolismo , Enfermedad Crónica , Femenino , Intercambio Iónico , Infarto del Miocardio/sangre , Infarto del Miocardio/orina , Miocardio/metabolismo , Neurotransmisores/sangre , Concentración Osmolar , Ratas , Ratas Endogámicas , Renina/sangre , Sodio/sangre , Sodio/metabolismoRESUMEN
1. The relationship between plasma atrial natriuretic peptide (ANP) and body sodium was determined in rats 1 month after myocardial infarction induced by coronary artery ligation. After operation rats received a normal or a low salt diet, and total exchangeable body sodium was measured sequentially. 2. Rats with infarction receiving a normal salt intake did not retain sodium when compared with sham-operated controls. Rats receiving a low salt diet had a 10% decrease in body sodium (P less than 0.01). The decrease was the same in rats with infarction as in controls. 3. Plasma ANP was similar in control rats irrespective of salt status. Plasma ANP levels were markedly elevated in rats with infarction irrespective of salt status (P less than 0.01). 4. The rise in plasma ANP was correlated with cardiac hypertrophy and infarct size in animals fed both normal and low salt diets. However, there was no relationship between plasma ANP and exchangeable body sodium. 5. These results suggest that in this model of heart failure plasma ANP is raised by increased left atrial stretch in proportion to the severity of left ventricular dysfunction. In contrast, plasma ANP concentrations do not appear to be elevated as a consequence of increased right atrial pressure caused by sodium retention and expanded extracellular volume.
Asunto(s)
Factor Natriurético Atrial/sangre , Infarto del Miocardio/metabolismo , Sodio/metabolismo , Animales , Enfermedad Crónica , Vasos Coronarios , Dieta Hiposódica , Femenino , Ligadura , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
1. The natriuretic and diuretic effects of three atrial natriuretic peptide (ANP) infusion rates were examined in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. 2. The natriuretic and diuretic effects of ANP were observed in controls and rats with infarction, but the effects were significantly attenuated in the latter. 3. Rats with chronic left heart failure were less sensitive to the renal effects of ANP compared with controls. 4. Impaired sodium and water excretion in chronic heart failure may be due partly to an attenuated renal response to ANP.
Asunto(s)
Factor Natriurético Atrial/farmacología , Insuficiencia Cardíaca/fisiopatología , Riñón/efectos de los fármacos , Animales , Factor Natriurético Atrial/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Enfermedad Crónica , Vasos Coronarios/fisiología , Diuresis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Infusiones Intravenosas , Infarto del Miocardio/fisiopatología , Natriuresis/efectos de los fármacos , Ratas , Ratas EndogámicasRESUMEN
1. Diabetes was induced in 32 adult Wistar-Kyoto rats with streptozotocin (60 mg/kg). Fourteen rats remained untreated, 10 received insulin three times per week, and eight received insulin daily. Fourteen non-diabetic rats served as controls. 2. Exchangeable sodium and plasma volume were elevated in the untreated diabetic rats. Treatment normalized these parameters. 3. Glomerular filtration rate (GFR) was elevated in the untreated diabetic group and the group receiving insulin three times per week compared with the control group. Daily insulin treatment restored GFR towards control values. 4. Plasma atrial natriuretic factor was similar in untreated diabetic rats and non-diabetic rats.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Tasa de Filtración Glomerular/efectos de los fármacos , Animales , Factor Natriurético Atrial/sangre , Volumen Sanguíneo/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Insulina/uso terapéutico , Ratas , Ratas Endogámicas WKY , Sodio/metabolismoRESUMEN
Plasma atrial natriuretic peptide levels are increased in heart failure. In rats with experimental heart failure, the elevation in plasma atrial natriuretic peptide bore a close relationship to the size of the myocardial infarct and the degree of ventricular dysfunction. Sodium retention, assessed by changes in exchangeable body sodium, could not be demonstrated in this model of cardiac dysfunction. Even rats receiving a low-sodium diet had increased plasma atrial natriuretic peptide levels following coronary artery ligation despite a significant decrease in exchangeable body sodium. This establishes that the elevated plasma atrial natriuretic peptide levels found in heart failure are a consequence of ventricular dysfunction and increased intracardiac pressures rather than a reflection of the salt and water status. Alternatively, the elevated plasma atrial natriuretic peptide may limit salt and water retention in this model. In these animals with high circulating atrial natriuretic peptide levels, "down-regulation" of renal atrial natriuretic peptide receptors could be demonstrated. This decrease in renal atrial natriuretic peptide receptor numbers may, in part, explain the blunted response to infused atrial natriuretic peptide in heart failure. However, changes in renal atrial natriuretic peptide receptors alone would appear to be insufficient to lead to salt and water retention without the activation of other sodium-retaining mechanisms that occur with the progression of cardiac failure. Nevertheless, this down-regulation of renal atrial natriuretic peptide may then contribute to the salt and water retention that occurs in congestive biventricular heart failure. The close relationship between increases in atrial natriuretic peptide and ventricular dysfunction rather than sodium balance suggests that atrial natriuretic peptide's primary role in the circulation may be to produce venodilation and increase capillary permeability. This may act rapidly to reduce cardiac preload and prevent pulmonary congestion. Vasodilation and natriuresis may then become supplementary actions to maintain cardiac output and remove the excess fluid.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Insuficiencia Cardíaca/metabolismo , Corazón/fisiopatología , Animales , Factor Natriurético Atrial/sangre , Factor Natriurético Atrial/fisiología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Riñón/metabolismo , Miocardio/patología , Ratas , Receptores del Factor Natriurético Atrial , Receptores de Superficie Celular/metabolismo , Renina/sangre , Sodio/metabolismoRESUMEN
The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantitation of receptors was performed by computerized in vitro autoradiography with 125I-labeled alpha-rat ANP (1-28) as the radioligand. When compared with controls, rats with myocardial infarction had markedly elevated plasma immunoreactive ANP concentrations (462 +/- 82 versus 124 +/- pg/ml, p less than 0.01) and reduced densities of ANP binding in the inner renal medulla (2.93 +/- 0.19 versus 3.53 +/- 0.22 fmol/mg protein, p less than 0.01). Extensive myocardial infarction was associated with a significant decrease in receptor numbers in the inner medulla (33.6 +/- 5.7 versus 95.6 +/- 9.6 fmol/mg protein, p less than 0.01) without significantly altering the affinity constant (1.76 +/- 0.51 versus 1.03 +/- 0.15 x 10(9) M-1, p greater than 0.05). Right ventricular weight increased in proportion to infarct size (r = 0.71, p less than 0.01), and both were correlated with plasma immunoreactive ANP levels (r = 0.74, p less than 0.01 and r = 0.75, p less than 0.01, respectively). Binding densities in the inner medulla of rats with infarcts were negatively correlated with right ventricular weight, plasma immunoreactive ANP concentrations, and also with infarct size (r = -0.92, p less than 0.001; r = -0.78, p less than 0.001; r = -0.77, p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Factor Natriurético Atrial/metabolismo , Enfermedad Coronaria/metabolismo , Médula Renal/metabolismo , Animales , Infarto del Miocardio/metabolismo , Miocardio/patología , Tamaño de los Órganos , Ratas , Ratas Endogámicas , Receptores del Factor Natriurético Atrial , Receptores de Superficie Celular/metabolismoRESUMEN
1. Changes in plasma atrial natriuretic peptide (ANP) were examined in conscious rabbits in response to a 33% blood volume expansion in intact animals and after blockade of cardiac nerve activity. 2. Blood volume expansion by one-third markedly increased right atrial pressure and resulted in a four-fold increase in plasma ANP. 3. Cardiac nerve blockade with intrapericardial procaine had no effect on resting plasma ANP levels. The ANP responses to volume expansion in the presence of cardiac nerve blockade were similar to those seen in intact animals. 4. Release of ANP from its cardiac stores in response to volume expansion is not influenced by cardiac nerve activity.
Asunto(s)
Factor Natriurético Atrial/metabolismo , Corazón/inervación , Miocardio/metabolismo , Animales , Volumen Sanguíneo , Femenino , Masculino , Presión , Procaína/farmacología , Conejos , RadioinmunoensayoRESUMEN
Congestive cardiac failure causes activation of various neurohumoral responses that increase total peripheral resistance and promote salt and water retention. These effects increase blood pressure and organ perfusion in the short term, but ultimately cause further cardiac decompensation by increasing ventricular afterload and cardiac work. The role of the renin-angiotensin-aldosterone system and the catecholamines is partially understood, and blockade of these systems as a treatment of heart failure is now established. The role of vasopressin in heart failure is more controversial, but there is now compelling evidence that vasopressin may have important vasoconstrictor actions in addition to its fluid retaining properties. Atrial natriuretic factor is a newly described cardiac hormone released from the atrium. Atrial natriuretic factor causes natriuresis, diuresis, vasodilatation, suppression of thirst, and suppression of both renin and aldosterone. These actions largely counteract the effects of the renin-angiotensin system and vasopressin. Plasma atrial natriuretic factor has been reported to be markedly elevated in human and experimental heart failure, and may act to limit the neurohumoral response to reduced cardiac output. This review summarizes our understanding of the vasoactive hormones and reports experimental evidence supporting a pathophysiological role for vasopressin and atrial natriuretic factor in congestive cardiac failure.