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Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. This role of endothelin-1 is unrelated to its plasma levels. The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction.

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The data indicate that in patients with severe systolic left ventricular dysfunction, the progressive left ventricular dilatation was accompanied by a decrease in left ventricular chamber stiffness; enalapril therapy was able to prevent or partially reverse these changes and tended to reduce left ventricular mass and ventricular sphericity. Those changes were suggestive of partial reversal of left ventricular remodeling by enalapril administration.

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The purpose of this study was to examine the effects of endothelin-1 (ET-1) on "diastolic stunning" in the postischemic myocardium. In 14 conscious dogs receiving either placebo (n = 7) or ET-1 (2.5 ng.kg-1.min-1, n = 7), left ventricular (LV) hemodynamics and regional wall motion (systolic segmental shortening by sonomicrometry and the ischemic-nonischemic regional asynchrony during isovolumic relaxation) were assessed at baseline, during 10 min of left anterior descending coronary artery occlusion (CAO) and at 60 min after reflow (R-60). During CAO, the ischemic segment shortening was severely depressed and both regional asynchrony and LV relaxation time constant were significantly increased in the placebo and ET-1 groups. At R-60, this LV diastolic dysfunction recovered to baseline conditions in the placebo group but was still present in the ET-1 group. Because coronary and myocardial blood flow returned to the baseline level at R-60 in both groups, the deleterious effects of ET-1 on diastolic stunning are probably mediated by its direct action on the myocardium.

Octreotide inhibits the secretion of several hormones and exerts vasopressor effects. To clarify the mechanism of atrial natriuretic factor (ANF) secretion and to assess the cardiovascular effects of octreotide in relation to changes in vasoactive peptide secretion, four groups of conscious dogs were studied: group I (n = 11) received saline infusion after placebo, group II (n = 10), the same infusion after octreotide, group III (n = 10), placebo only and group IV (n = 10) octreotide injection only. Saline (10% body wt) was infused over 40 min after subcutaneous injection of placebo or octreotide (1 microgram/kg). Saline produced a rise (p < 0.001) of plasma ANF from 32.4 +/- 4.1 to 59.0 +/- 8.5 pM after placebo and from 35.6 +/- 5.5 to 77.0 +/- 12.6 pM after octreotide. This rise, not significantly different between groups I and II paralleled a 4-5-fold increase (p < 0.005) of right and left atrial pressures. With a higher dose of octreotide (4 micrograms/kg) injected in 4 dogs, plasma ANF increased by 27.5 +/- 5 pM. During hypervolemia, plasma endothelin-1 remained unchanged but plasma angiotensin II and epinephrine decreased (p < 0.05) approximately by 80% without being affected by octreotide. Octreotide did not influence the basal secretion of ANF, endothelin-1, angiotensin II and catecholamines. However, in basal conditions, octreotide injection resulted in a 9% increase (p < 0.005) of left ventricular systolic pressure, unobserved after placebo. Plasma glucose decreased (p < 0.005) in groups receiving octreotide. Thus, octreotide does not impair the stretch-mediated release of ANF which implies a release mechanism independent from somatostatin receptors and consequent changes in intracellular c-AMP. Octreotide has also a pressor effect, unrelated to changes in vasoactive peptide production.

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