The effect of left ventricular hypertrophy (LVH) due to chronic pressure overload on right atrial (RA) and left ventricular (LV) myocardial beta-adrenergic receptor (beta-AR) density and subtypes, adenylyl cyclase (AC) activity and ADP-pertussis toxin ribosylated proteins was investigated in humans with LVH due to aortic stenosis and in patients without LVH undergoing heart surgery for mitral stenosis or coronary artery disease taken as controls. Both groups presented normal systolic function or plasma catecholamine levels. In LVH and controls, beta-AR density was similar in RA (62 +/- 6 vs 77 +/- 12 fmol.mg-1 protein) and LV (39 +/- 7 vs 32 +/- 2 fmol.mg-1 protein). In LVH, beta 1-AR percentage was < than in controls in LV (35 +/- 11 vs 73 +/- 5%, P < 0.05) but not in RA (79 +/- 5 vs 73 +/- 8%). Basal AC activity in RA (19 +/- 4 vs 21 +/- 6 pmol.mg-1 protein) and LV (22 +/- 5 vs 27 +/- 3 pmol.mg-1 protein) was similar in LVH and in controls. Isoprenaline-induced stimulation of AC in RA was similar in LVH and in controls (51 +/- 18 vs 36 +/- 18%) but < in LV of LVH (7 +/- 6 vs 45 +/- 6%, P < 0.05). In the presence of ICI-118,551 (a beta 2-adrenoceptor antagonist), isoprenaline failed to induce any increase in cAMP in LVH. The quantification of ADP-pertussis toxin ribosylated proteins indicated a lower concentration of substrates in LV myocardial membranes from LVH. These data indicate that in LVH due to pressure overload, there is a down-regulation of beta 1-AR and an increase in beta 2-AR density. This is associated with alterations of the transmembrane signalling marked by a decreased capacity of isoprenaline to stimulate AC and an impaired expression of Gi proteins.

1 Ten patients with acute myocardial infarction and left ventricular failure were studied. Acute myocardial infarction was anterolateral in eight patients, posterolateral in one, and anteroseptal in one. Three patients were grade II, 4 grade III, and 3 grade IV of Killip's classification. None presented with arterial hypertension but mean values of plasma renin activity and serum aldosterone were 20.7 ng/ml/h and 13.5 ng/100 ml. Haemodynamic measurements were performed by using a flow-directed catheter. Cardiac output was determined in triplicate by thermo-dilution (Edwards computer). Classic haemodynamic measurements included: heart rate, cardiac index, stroke volume index, stroke work index, blood pressure, right atrial pressure, pulmonary vascular resistance, systemic vascular resistance, and pulmonary diastolic blood pressure. Curves of ventricular function correlating stroke work index and pulmonary diastolic blood pressure were constructed. Haemodynamic changes after drug therapy were tested for significance using the paired t test. All patients received heparin, oxygen, and an intravenous infusion of isosorbide dinitrate. 2 Haemodynamic measurements were repeated at 30 min intervals and after isosorbide infusion until values returned to normal. The infusion was then discontinued and pressures returned to control values. At this time, oral captopril was administered, the first dose being 12.5 mg. Subsequent doses of 12.5 mg up to 50 mg were given if systolic blood pressure remained above 100 mm Hg and pulmonary diastolic pressure greater than 18 mm Hg. When the most effective oral dose was determined it was administered at six hourly intervals. This therapy resulted in an improvement of functional class, with a reduction in Killip's grade from class III to 1.7 (mean value). Heart rate, mean atrial pressure, and pulmonary diastolic pressure decreased by 10%, 32% and 41%. Cardiac index increased from 2.4 + 0.8 I/min/m2 to 2.8 (p < 0.02) and stroke volume index increased by 37.2%. Pulmonary vascular resistance decreased by 22.14% (p < 0.001) and the product of heart rate x blood pressure decreased by 33.6% (p <0.001).3 Haemodynamic effects of oral captopril treatment were beneficial in left ventricular failure and acute myocardial infarction without immediate side effects. In acute left ventricular failure the renin angiotensin system was appreciably stimulated. All ten patients who were treated for a mean of 6.5 days showed a significant subjective, clinical, and haemodynamic improvement. After discharge from the coronary care unit anterolateral infarctions produced by ventricular fibrillation resulted in four deaths. 4 These data suggest that captopril may be an effective therapy in acute myocardial infarction with left ventricular failure and that it is more effective than other vasodilators. Nevertheless, more patients need to be studied for a longer period before definite conclusions can be drawn.

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