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Acute ETA blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.

Objective-To examine the contribution of endothelin type A (ET A ) receptor stimulation by endogenously generated endothelin-1 (ET-1) to the maintenance of coronary vascular tone in humans. Design-Controlled clinical study. Setting-Tertiary cardiovascular referral centre. Patients-14 subjects were studied, seven with normal coronary arteries and seven with coronary artery disease, mean (SEM) age, 53 (2) years. Interventions-After diagnostic coronary arteriography, BQ-123 (a selective ET A receptor antagonist; 100 nmol/min) in 0.9% saline, was infused into the left coronary artery at a rate of 1 ml/min for 60 minutes. Eight control subjects received saline alone. Main outcome measures-Blood flow velocity in the left anterior descending coronary artery, measured using a Doppler flow guidewire; coronary arteriography performed at baseline and immediately at the end of the BQ-123 or saline infusion to measure the diameter of proximal and distal left anterior descending coronary artery segments. Results-The diameter of the proximal segment increased by 6 (2)%, while that of the distal segment increased by 12 (3)% after BQ-123 (both p < 0.05 v baseline). Coronary blood flow increased from 75 (10) to 92 (10) ml/min and coronary vascular resistance decreased from 1.99 (0.36) to 1.44 (0.22) mm Hg/ml/min after BQ-123 (both p < 0.05 v baseline). The response to BQ-123 of patients with and without coronary artery disease was similar. There was no eVect of saline in the controls. Conclusions-Endogenously produced ET-1 contributes to the maintenance of basal coronary artery tone in humans by ET A receptor stimulation. The role of ET B receptors remains to be defined. (Heart 2000;84:176-182) Keywords: endothelins; arteries; blood flow; coronary circulation; angiographyThe endothelins are a family of 21 amino acid peptides with potent and characteristically sustained vasoconstrictor and vasopressor actions.1 Endothelin-1 (ET-1) is the predominant isopeptide generated by the vascular endothelium.2 ET-1 binds to at least two receptors. The ET A receptor appears to be the major one, causing vasoconstriction in arteries, while the ET B receptor mediates the release of endothelium dependent vasodilator substances and is also present in some resistance and capacitance arteries, where it can contribute to vasoconstriction.3 ET-1 may play a role in the pathophysiology of several conditions associated with vasoconstriction, including chronic heart failure, hypertension, Raynaud's disease, and renal failure.3 4 Recently described inhibitors of endothelin converting enzyme and endothelin receptor antagonists may therefore have therapeutic potential as vasodilator drugs in these conditions. Endogenous production of ET-1 contributes importantly to the maintenance of basal peripheral vascular tone 5 and blood pressure 6 in healthy volunteers, mainly through an eVect on ET A receptors. In contrast, the main eVect of endogenous ET-1 on ET B receptors in resistance arteries appears to be vasodilatation. ET-1 constricts human epicardi...

SummaryBackground: Increased levels of plasma brain natriuretic peptide (BNP) are observed in patients with congestive heart failure, hypertension, left ventricular hypertrophy, and acute myocardial infarction. However, there are no data on serial changes in plasma levels of BNP in patients undergoing coronary angioplasty.Hypothesis: The study was undertaken to examine plasma concentrations of BNP together with those of atrial natriuretic peptide (ANP) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA).Methods: Plasma concentrations of BNP and ANP were examined in 13 patients with stable anginapectoris and good left ventricular function undergoing PTCA. Blood samples were taken from the femoral vein at baseline, after the first balloon inflation, after the end of the procedure, and 4 h thereafter.Results: Plasma BNP levels were 14 k 4 at baseline, 22 2 10 after the first balloon inflation, 28 f 12 at the end of the procedure, and 15+4pgr/ml4hthereafter(F= 13.05,p