Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.

Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age-matched men with typical Type B behavior pattern. Twenty-four hour urine collections were divided into three periods: 9AM - 6PM , 6PM to bedtime, and bedtime to 9AM . Type A men showed a significantly higher excretion than Type B men in the daytime ( 9AM - 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.

Hepatic cholesterol-7alpha-hydroxylase activity in neurogenic hypercholesterolemia.

The cholesterol-7alpha-hydroxylase activity of hepatic microsomal preparations of hypothalamic hypercholesterolemic rats and normal rats was assayed in rats fed diets high and low in cholesterol, and in rats killed at the supposed height and at the nadir of the diurnal cycle of enzyme activity. The activity of this enzyme system appeared to be unimpaired in the hypothalamic hypercholesterolemic rat.

Neurogenic hypercholesterolemia: influence of autonomic drugs.

Eleven substances capable of either augmenting or depleting the alpha- and - beta-adrenergic capacities of the autonomic nervous system were administered to rats exhibiting hypothalamic hypercholesterolemia and to normal controls. Only the beta-adrenergic blocking agents propranolol and possibly 6-OH dopamine were observed to alter (raise) the serum cholesterol concentration, and this occurred in both experimental and control animals. Neither atropine, nor the serotonin-depleting agent, rho-chlorophenylalanine, nor the serotonin-antagonist cyproheptadine, were observed to alter serum cholesterol level. Such absence of effect was also noted with metaraminol, phenoxybenzamine, isoproterenol, epinephrine, reserpine, and alpha-methyl tyrosine.

Phenobarbital as a hypocholesterolemic agent in the rat and rabbit.

The administration of phenobarbital was observed to inhibit the rise in serum cholesterol that occurred in rats after thyroidectomy or hypophysectomy and in rabbits after inclusion of cholesterol in their diet. This hypocholesterolemic effect of phenobarbital was found to be due to its capacity to inhibit the intestinal absorption of cholesterol in both these species. We found no evidence to suggest that phenobarbital altered the endogenous process of cholesterol metabolism in either of these two species of animals.

Further studies concerning glucagon-induced hypocholesterolemia.

Some of the possible mechanisms responsible for the hypocholesterolemic effect of glucagon were investigated. Glucagon was found to inhibit the intestinal absorption of cholesterol. In addition, it was found to either hasten the rate of egress of lipoprotein cholesterol from the blood into the liver or to retard the rate of re-entry of cholesterol from the liver into the blood. The data do not distinguish between these two possibilities, which indeed may occur simultaneously.

A precise catecholamine assay for small plasma samples.

The time, temperature, and pH of the trihydroxyindole reaction were controlled to minimize interference between norepinephrine (NE) and epinephrine (E) so that, in plasma catecholamine assay within normal human physiologic range, NE contributes less than 1 per cent to the fluorescence produced from E, and E contributes only 0.5 to 10 per cent to NE fluorescence; assay and blank measurements show superior stability. Elution from alumina and instrumental factors, such as optical filters, were optimized so that a single 5 ml. plasma sample sufficed for triplicate analyses of both NE and E, with duplicate blanks for each. This triplicate fluorescence assay was combined with duplicate recovery measurements of radioactive catecholamines added in tracer quantities to the plasma so as to make possible reliable estimates of the precision of measurement of each individual sample. The mean levels found for men aged 40 to 60 years from antecubital vein blood drawn during the subject's working hours (but after a brief rest) were, for NE 0.38 ng. per milliliter, range 0.15 to 0.54 ng. per millilter, and for E 0.09 ng./ml, range 0.01 to 0.27 ng. per millilter. The high precision and small amounts of blood required by this method made possible the measurement of basal plasma levels of E and NE in rats under two-stage phenobarbital anesthesia. The mean levels for 13 male and 4 female Long-Evans-stain rats weighing 250 to 350 grams were, for NE 0.26 ng. per millilter, range 0.16 to 0.37 ng. per millilter, and for E 0.36 ng. per millilter, range 0.14 to ng. per millilter. These rat values are called basal because they are only 1/5 to 1/10 as large as values obtained on plasma secured by single-stage pentobarbital anesthesia or from unanesthetized rats. Eight to 11 ml. of whole blood obtained from each rat were sufficient for individual analyses, an improvement over most other reported methods which require blood from a number of animals to be pooled. The average precision of an individual determination of NE was plus or minus 10 per cent in the range of 0.20 to 0.40 ng. per millilter. The average recovery for NE was 65 per cent and for E it was 55 per cent. Major factors influencing recovery were quantitatively investigated and discussed.

Plasma catecholamine response of coronary-prone subjects (type A) to a specific challenge.

Plasma norepinephrine (NE) and epinephrine (E) were assayed in 15 men prone to develop coronary heart disease (type-A behavior pattern) and in 15 coronary-disease-resistant men (type-B behavior pattern) under resting, noncompetitive conditions and also immediately before, during, and after participation in a nonphysical competitive struggle. The average concentration of catecholamines was virtually the same in both groups under resting conditions. Under competitive conditions the NE concentration of the coronary-susceptible group rose an average of 30%, while that of the resistant group remained essentially unchanged. E concentration remained unchanged in both groups.