The objective of the study was the evaluation of natriuretic peptides in ischemic heart disease. Atrial and brain peptides (ANP, BNP) were elevated in patients with ischemic heart failure, as compared with patients with angina without overt failure, and controls (p < 0.01). BNP/ANP ratio was higher in NYHA class IV than in class III patients (2.67 ± 0.87 vs. 1.52 ± 0.59, respectively). Patients in the angina group, in whom elevated BNP or ANP was found, had subclinical systolic or diastolic dysfunction. There was inverse correlation between BNP, ANP and the left-ventricular ejection fraction (each r = 0.78, p < 0.001). We conclude that BNP is elevated as a result of myocardial dysfunction, but not of ischemia and seems to be a better index of disease stage and prognosis than ANP.

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Eleven hypertensive patients in whom clonidine therapy had to be discontinued, were treated prophylactically with labetalol, in order to avoid a possible hypertensive crisis. Most of the known side effects, which are consistent with the withdrawal phenomenon were observed, e.g. tremor, insomnia and apprehension, but headaches and flushing did not occur. Blood pressure levels remained unchanged, despite up to a 20-fold increase in plasma catecholamines. The lack of change in serial measurements of plasma cyclic AMP level appears to indicate that adequate adrenergic blockade was induced by labetalol. Since labetalol is a potent anti-hypertensive drug, and is also effective in avoiding a possible hypertensive crisis due to withdrawal of clonidine, we propose to use it as the drug of choice whenever discontinuation of clonidine therapy is indicated.

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Hydralazine is a potent arteriolar dilator, which increases cardiac output in patients with heart failure. Previous studies suggested that these beneficial effects might be due in part to a positive inotropic effect. The present study further investigated the effect of hydralazine on myocardial contractility and adenyl cyclase activity. In isolated cat papillary muscles, bath concentrations of hydralazine up to 10(-4) mol X litre-1 did not alter force development, whereas 10(-3) mol X litre-1 hydralazine increased isometric force by 31%. This effect was blocked by 10(-6) mol X litre-1 propranolol and was absent after catecholamine depletion produced by previous reserpine treatment. In canine ventricular myocardium hydralazine in all concentrations used (10(-7) to 10(-3) mol X litre-1) increased control adenyl cyclase activity. This increase was statistically significant in 10(-6) to 10(-3) mol X litre-1 concentrations, reaching a maximum of 69.5% at 10(-4) mol X litre-1. In cat ventricular myocardium 10(-6) to 10(-3) mol X litre-1 hydralazine increased the cyclic AMP production, although to a lesser magnitude than that in canine tissue. Hydralazine 10(-5) mol X litre-1 produced a 37.8% increase, and the maximum effect of 45.2% occurred at 10(-3) mol X litre-1. The positive effects of hydralazine were completely abolished by the addition of propranolol in dogs as well as in cats. Thus the adenyl cyclase stimulation induced by hydralazine is mediated through the beta receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocytes of patients with polycythemia vera exhibited increased activity of oxidative pentose shunt, accelerated generation of phosphoribosylpyrophosphate, increased incorporation of ¹⁴C-adenine into nucleotides, and increased activity and thermostability of adenine-phosphoribosyltransferase. These abnormalities are attributed to age dependency of the pathways concerned and presence in polycythemia vera of an erythrocyte population younger than normal.

The activity of metabolic pathways involved in the formation and utilization of phosphoribosylpyrophosphate (PRPP) was studied in the erythrocytes of 34 patients with idiopathic metabolic gout. The activities of the oxidative pentose shunt, of the hypoxanthine-guanine and adenine phosphoribosyltransferases (HGPRT, APRT) and of PRPP synthetase, as well as the rates of PRPP generation and of adenine incorporation into nucleotides were found to be normal in the erythrocytes of all these patients. Four patients with metabolic gout due to enzymatic abnormalities, two relatives with partial deficiency of HGPRT and two relatives with mutant feedback-resistant PRPP synthetase, were studied for comparison. The significance of the results is discussed in relation to postulated mechanisms for purine overproduction in metabolic gout.

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