[The best of hypertension in 2004]. / L'essentiel de 2004 en hypertension artérielle.

Among the major developments of the year 2004 in the knowledge of hypertension, a special part should be dedicated to the venue in Paris of the Fourteenth meeting of the European Society of Hypertension last June. Beside major progress observed in basic science, namely signaling pathways involved in the regulation of smooth muscle tone, growth and inflammation, at the cross-road of hypertension, diabetes, and metabolic syndrome, large clinical trials have afforded strong evidence for the usefulness of lowering blood pressure in various diseases associated with hypertension. Despite these advances, the percentage of treated hypertensive patients who reach the BP goal (<140/90 mmHg) is too low (about 30%). Thus urges the need for adapting therapeutic strategies. The ESH meeting gave the opportunity to gather a large body of evidence for a better therapeutic approach, in order to control BP in a larger number of hypertensive patients.

[Role of endothelium-derived nitric oxide in sustained flow-dependent dilatation of human peripheral conduit arteries]. / Rôle du monoxyde d'azote dans la dilatation débit-dépendante des artères de conductance périphériques en réponse à une stimulation soutenue.

Endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases and is generally associated to the decrease in arterial nitric oxide (NO) availability. In humans, endothelial function can be evaluated by the post-ischaemic flow-dependent dilatation (FDD) of peripheral conduit arteries which is mainly mediated by the NO release when short duration of reactive hyperaemia are used (3 to 5 min ischaemia). However, recent studies suggest that the role of NO in this response decreases as the duration of the hyperaemic stimulation increases. The aim of the present study was thus, to evaluate, in healthy subjects, the role of NO in the FDD of conduct arteries in response to a sustained stimulation. Radial artery diameter (echotracking) and flow (Doppler) were measured, 7 cm under the elbow line, at baseline and during post-ischaemic hyperaemia (10 min wrist cuff inflation) in 10 healthy subjects (age: 24 +/- 1 years) in control period and after acute blockade of the endothelial NO-synthase by local infusion of NG-monomethyl L-arginine (L-NMMA, brachial artery, 8 mumol/min, 7 min). Endothelium-independent dilatation was studied by mean of sodium nitroprusside infusion (SNP: 5, 10 and 20 nmol/min, 3 min each dose before and after L-NMMA). L-NMMA administration decreased radial artery blood flow at base (Control: 14 +/- 2 vs L-NMMA: 10 +/- 1 ml/min, P < 0.05) and increased radial artery vasodilatation in response to SNP (P < 0.05) thus, demonstrating NO-synthase inhibition. Therefore, after L-NMMA there was a small decrease in radial FDD (Control: base: 2.52 +/- 0.05 mm, FDD: 11.3 +/- 0.6% vs L-NMMA: base: 2.51 +/- 0.04 mm: FDD: 9.0 +/- 0.9%; p < 0.05) without change in hyperaemia. In conclusion, our results demonstrate, in contrast to those obtained after short duration of hyperaemia, that the relative implication of NO in the flow-dependent vasodilatation of peripheral conduit arteries in humans decreases in response to sustained stimulation and suggest, in these experimental conditions, an associated flow-dependent vasodilating mechanism that is unaffected by the NO-synthase inhibition.

Emerging concepts of neurohumoral modulation in the treatment of congestive heart failure.

The angiotensin converting enzyme (ACE), endothelin (ET) converting enzyme (ECE) and neutral endopeptidase (NEP) are all zinc-metallopeptidases expressed in almost all the organs, such as heart, vessels and kidneys. While ACE and ECE are respectively involved in the transformation of angiotensin I and Big-ET into angiotensin II and ET-1 respectively, which possess vasoconstrictor and mitogenic properties, NEP is involved in the degradation of atrial natriuric factor (ANF), which possesses vasorelaxant, diuretic/natriuretic and antihypertrophic properties. These three systems are activated in heart failure and modulate the progression of heart failure. This article will discuss preliminary date concerning simultaneous inhibition of ACE, ECE and/or NEP and their therapeutic potential interest in the treatment of heart failure.