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Biomedical subjects

J F Arnal

Publications and source records attributed to J F Arnal.

11 recordsLinked to original sources
PubMed1992

[Usefulness of converting enzyme inhibitors in the diagnosis of arterial hypertension].

Angiotensin-converting enzyme (ACE) inhibitors are now widely used as first-line treatment of essential hypertension. Their effectiveness is potentiated by a low-salt diet and, above all, by the simultaneous prescription of diuretics. When secondary hypertension is suspected, ACE inhibitors are a good pharmacological tool to study the renin-angiotensin system. Since activation of this system is the main mechanism responsible for renovascular hypertension, ACE inhibitors are very useful for diagnosis. Conversely, blood pressure is not influenced by ACE inhibitors in primary hyperaldosteronism because of the low plasma renin and angiotensin II levels. Pheochromocytoma activates the renin-angiotensin system, and ACE inhibitors combined with beta-blockers enable the hypertension to be controlled prior to surgical treatment of the tumour. Finally, ACE inhibitors can be used to explore the renin-angiotensin system in the experimental model of renovascular hypertension and therefore contribute to our knowledge of the complex pathophysiology of this most frequent type of secondary hypertension.

Adrenal Gland Neoplasms↗
PubMed1992

[Signals regulating arterial vasomotricity and vasotrophicity].

Second messengers regulating the level of free intracellular calcium and the level of phosphorylation (kinase activities) transduce within the cells the mechanical and biochemical (endocrine, paracrine and autocrine) signals detected by the arterial wall. In arterial smooth muscle cells two signalling pathways produce opposite functional and structural effects: the breakdown of phosphoinositol leading to an increase in intracellular calcium level, and the cyclic guanosine monophosphate (GMP) pathway resulting in a decrease in calcium level. The arterial cyclic GMP pathway is predominantly under control of the endothelial function to secrete no rather than influenced by the atrial natriuretic factor. These two intracellular second messenger pathways are involved not only in the regulation of motricity, but also in the control of arterial wall trophicity, including hypertrophy, hyperplasia and collagen hypersecretion. Inactivation of the cyclic GMP pathway and activation of phosphoinositol breakdown predominate in vascular adaptation to the ageing process.

Angiotensin II↗
PubMed1992

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity.

Amino Acid Oxidoreductases↗
PubMed1992

[Double-blind clinical and echocardiographic study of oral enoximone versus placebo in severe cardiac insufficiency].

The effect of enoximone was assessed by a randomised double blind trial versus placebo. The clinical status of the patients was evaluated by the NYHA classification and quality of life score. Inotropic state was estimated from the maximum acceleration of aortic and pulmonary blood flow recorded by Doppler echocardiography. Thirty patients with severe cardiac failure, aged 66.4 +/- 14 years, symptomatic despite maximal therapy associating diuretics, digitalis, nitrate derivatives and angiotensin converting enzyme inhibitors, were included. Fifteen patients were given enoximone 100 mg three times a day orally (Group E) and the other 15 were given a placebo (Group P). The NYHA class and quality of life scores were assessed at D0, D4 and D31. Doppler echocardiography and Holter recordings were performed on D0 and D31. The two groups were comparable at D0. Ten patients abandoned the trial, 3 from Group E (including 1 death) and 7 from Group P (including 3 deaths). At D4, 13 patients from Group E and 8 from Group P were clinically improved (p < 0.05). At D31, the clinical state was stable or improved in 10 of the 12 patients in Group E and 6 of the 8 patients in Group P (NS). No secondary effects were severe enough to warrant the withdrawal of treatment: the frequency of ventricular extrasystoles was comparable in the two groups at D0 and D31. At D31 the maximal aortic acceleration had increased by 20% compared with D0 (p < 0.05) and the maximal pulmonary acceleration by 31% (p < 0.05) in Group E. The same parameters showed no significant change in Group P (-6% and +5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

[Correlations between plasma concentrations of atrial natriuretic factor and right ventricular function in patients with severe cardiac failure].

The atrial natriuretic factor (ANF) is secreted by the atria in mild and moderate cardiac failure but, during the evolution of the cardiac failure, the ventricles are also recruited and secrete ANF. In order to investigate the relation between plasma ANF and Doppler echocardiographic parameters of severe cardiac failure, the concentrations were measured simultaneously in 20 patients with NYHA Class III and IV cardiac failure (10 due to ischaemic and 10 due to primary dilated cardiomyopathy) despite optimal medical treatment including an angiotensin converting enzyme inhibitor. Overall, there was a weak negative correlation between the plasma ANF concentrations and the decrease in right ventricular surface area (r = -0.58, p less than 0.005, n = 20 patients). This relation was highly significant in ischaemic cardiomyopathy (r = -0.81, p less than 0.002, n = 10 patients) and not significant in primary dilated cardiomyopathy (r = -0.29, NS, n = 10 patients). No relationship was observed between plasma ANF and other echocardiographic parameters (atrial surface area, right and left ventricular dimensions, left ventricular ejection fraction and mass) or with Doppler aortic indices (acceleration, maximum and mean velocities, aortic velocity-time integrals). However, plasma ANF was related to the velocity of mitral regurgitant jets (r = -0.70, p less than 0.01) which is dependent on left ventricular pump function. These results show that plasma ANF concentrations are only related to right ventricular systolic function and the velocity of mitral regurgitation in patients with severe cardiac failure.

Adult↗
PubMed1991

Low angiotensinogen levels are related to the severity and liver dysfunction of congestive heart failure: implications for renin measurements.

PURPOSE: To compare the determination of plasma renin activity (PRA) and the direct measurement of active renin by immunoradiometric assay (IRMA) as methods of assessing the renin system in patients with congestive heart failure. PATIENTS AND METHODS: The status of the renin-angiotensin system in congestive heart failure was assessed by measuring the plasma renin substrate concentration, PRA, and plasma concentration of active renin in 37 patients with mild to severe congestive heart failure. Natremia and plasma levels of atrial natriuretic factor (ANF) were determined as biologic indexes of the severity of heart failure, and concentrations of prealbumin and retinol-binding protein were used as indexes of liver dysfunction. RESULTS: The PRA and the concentrations of active renin and ANF were markedly higher in patients with New York Heart Association class IV heart failure than in patients with class II to III heart failure, while natremia and the concentrations of renin substrate, prealbumin, and retinol-binding protein were markedly lower in the class IV patients than in the class II to III patients. Plasma renin substrate concentration was negatively correlated with active renin concentration (n = 37, r = -0.45, p = 0.005), and positively related to natremia (r = 0.56, p less than 0.0005), prealbumin (r = 0.54, p less than 0.001), and retinol-binding protein (r = 0.60, p less than 0.0001). CONCLUSIONS: Low levels of plasma renin substrate can be considered as an indirect index of the severity of heart failure that reflects both the high level of circulating active renin and the decrease in hepatic protein output. In patients with class IV heart failure, low levels of renin substrate led to a marked underestimation of active renin concentration from measurements of PRA. In contrast, direct IRMA of active renin measures the true plasma active renin concentration, independent of plasma renin substrate, and closely reflects renin secretion.

Adult↗
PubMed1991

[Recent advances in the investigation of the renin-angiotensin and cardiac natriuretic systems in patients with chronic heart insufficiency].

The renin-angiotensin and cardiac natriuretic systems were studied by measuring plasma renin activity, plasma concentrations of active renin, angiotensinogen, atrial natriuretic hormone and urinary cyclic GMP in 37 patients with moderate to severe cardiac failure. The plasma sodium and osmolality were chosen as markers of hydroelectrolytic imbalance and plasma concentrations of préalbumin and retinol-binding protein as indicators of the degree of hepatocellular dysfunction. Plasma renin activity (PRA) plasma concentration of active renin, atrial natriuretic hormone and urinary cyclic GMP were higher in patients in NYHA Class IV than in those in Classes II-III, whilst plasma sodium, angiotensinogen, prealbumin and retinol-binding protein concentrations were lower in Class IV patients than in patients in Classes II-III. The plasma angiotensinogen concentrations were negatively correlated with PRA (r = -0.41, p less than 0.02), active renin (r = -0.45, p = 0.005), the atrial natriuretic factor (r = -0.36, p less than 0.05) and positively correlated with prealbumin (r = 0.54, p less than 0.001) and retinol-binding protein (r = 0.60, p less than 0.0001). In NYHA Class IV patients the decreased circulating renin substrate led to an underestimation of plasma concentrations of active renin by measurement of PRA. On the other hand, direct radio-immunometric measurement of active renin allows true estimation of circulating active renin, independently of plasma angiotensinogen concentrations and thereby reliably reflects activation of the renin system. The serum sodium was negatively correlated with active renin (r = -0.66, p less than 0.0001) in these patients not receiving converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Immunoradiometric assay of active renin versus determination of plasma renin activity in the clinical investigation of hypertension, congestive heart failure, and liver cirrhosis.

We compared the determination of plasma renin activity (PRA) and the direct immunoradiometric measurement of active renin (AR) as ways of assessing the activity of the renin-angiotensin system in normal volunteers and in patients with hypertension, heart failure, or liver failure. The levels of plasma renin substrate, angiotensinogen, and the ratio of PRA to AR concentration did not differ in the normal volunteers and the patients with essential or renovascular hypertension. However, compared to the volunteers, patients with severe heart or liver failure had markedly reduced plasma renin substrate levels, which led to a considerable underestimation of AR concentration when it was measured by PRA.

Adult↗
PubMed1990

Atrial natriuretic factor as a marker in congestive heart failure.

Cardiac overload is associated with an overexpression of the atrial natriuretic-factor (ANF) gene in experimental models and in man. Sites of ANF gene overexpression are the atria but also the ventricular myocardium. This recruitment phenomenon of the ventricle to synthesise and secrete ANF is directly dependent on the increase in stress-stretch relationship in each cardiocyte. Therefore, the levels of plasma ANF and its second messenger, cyclic glycophosphate mutase in plasma and urine appear as markers of congestive heart failure in animal models and in man. Particularly, plasma ANF has been recognized recently as independent prognostic factor in congestive heart failure.

Atrial Natriuretic Factor↗
PubMed1990

[Atrial natriuretic factor. Current data and future perspectives].

The physiology, the pharmacology and the biochemistry of the atrial natriuretique factor (ANF) have been investigated and documented by numerous studies and works since its discovery and cloning ten years ago. More recently, the physiopathological aspect of ANF biosynthesis and secretion by the whole heart during overload and congestive heart failure was reported in experimental models and in human patients. Moreover the cyclic GMP which is the ANF second messenger, egressed from endothelial cells, was correlated with the production of ANF. Therefore the activation of heart endocrine function from ANF gene over-expression to peripheral cyclic GMP appeared as an independent prognosis indicator in congestive heart failure. Two types of ANF receptors have been recently cloned. One is the particulate guanylate cyclase, the second is a clearance receptor involved in the endocytosis and lysozomial degradation of ANF in target cells. Neutral endopeptidase, an ectoenzyme present in different tissues and particularly in the kidney is also capable to cleave ANF in unefficient peptide. The blockade of ANF metabolism by clearance receptor antagonists and neutral endopeptidase inhibitor potentializes the biological effect of exogenous and endogenous ANF particularly on the renal function. This approach of ANF metabolism-inhibition opens new ways on the future of ANF in cardiovascular therapeutic.

Atrial Natriuretic Factor↗