A phase I dose-response study of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl (MK-447) was performed with the following oral doses: 6.25, 12.5, 25, 50, and 100 mg. Each volunteer served as his own control. The study was carried out in double-blind fashion on a 5-Gm Na and K diet with a minimum 2000 ml fluid intake. Urine was fractionated and analyzed for sodium, chloride, potassium, calcium, uric acid, and volume. Comparisons (MK-447 minus control values) of the 24-hour total sodium, calcium, potassium, and volume excretion rates at 6.25, 25 and 100 mg MK-447 were as follows: sodium, 195, 345, and 528 muEq/min; chloride, 191, 365, and 756 muEq/min; potassium, 77, -3, and 65 muEq/min; and volumes, 1, 3.4 and 11.7 ml/min. MK-447 did not alter calcium excretion. Uric acid excretion was observed to decrease as the dose of MK-447 was increased, however, the serum uric acid level always remained within normal limits. MK-447 did not alter the physiologic parameters but did produce symptoms of volume contraction at 100 mg. Because no further dose increase was attempted, a plateau in the dose-response curve was not reached. Comparison of 100 mg MK-447 with 80 mg oral furosemide revealed similar potency and a somewhat longer duration of action for MK-447.

Butylated Hydroxytoluene↗

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Cardiovascular response to mental stress in normal adolescents with hypertensive parents. Hemodynamics and mental stress in adolescents.

The hemodynamic response to mental stress (mental arithmetic) was studied in adolscents with varying risk factors for essential hypertension (EH), One group (genetic) consisted of normotensive well adolescents who had at least one parentnt with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one pare with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (P less than THE CONTROL POPULATION (P LESS THAN 0.001). The stress response of the normotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p less than 0.001, less than 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension.

Adolescent↗

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Sequential hemodynamic changes in end-stage renal disease and the anephric state during volume expansion.

The sequence of hemodynamic events during periods of salt- and water-loading was studied in anephric patients and those with end-stage kidney disease. The 10 patients studied showed four different sequential hemodynamic patterns: 1) no significant increase in blood pressure (BP) in two patients; 2) increase in BP associated with an increase in cardiac output and without change in total peripheral resistance in two patients; 3) increase in BP associated with an increase in total peripheral resistance from the beginning without an increase in cardiac output in five patients; and 4) increase in BP associated with an initial increase in cardiac output followed by an increase in total peripheral resistance in one patient. There was a significant positive correlation between BP and blood volume and between BP and total exchangeable sodium in the patients in whom salt- and water-loading increased the BP. It is concluded that during salt- and water-loading an initial rise in cardiac output is not necessary to increase BP and that a sustained rise in cardiac output does not always increase the total peripheral resistance. Mechanisms other than whole-body autoregulation play a role in increasing BP during salt- and water-loading in patients deprived of renal excretory function.

Adolescent↗

PubMedDate not supplied

Cardiovascular characteristics in adolescents who develop essential hypertension.

The risk parameters for the development of essential hypertension (EH) were evaluated in a group of adolescents with borderline hypertension. A population comprised of 50 adolescents with systolic or diastolic blood pressure between the 90th and 95th percentile was compared to a normotensive (less than 90%) family history-negative control population. Evaluative parameters included genetic risk, resting blood pressure, resting heart rate, and cardiovascular response to mental stress. In a follow-up period of up to 41 months, 28 borderline hypertensive adolescents (56%) developed fixed EH. At the time of initial evaluation, these 28 hypertensive adolescents had a strong family history of EH, higher resting heart rate (p less than 0.01) and blood pressure (p less than 0.01), and a greater cardiovascular response to mental stress (p less than 0.001) compared to the normotensive family history-negative control population. Time series analysis of the stress phase also demonstrated a rhythmic cardiovascular response in the normotensive group (p less than 0.05) that was not present in the hypertensive group. These results indicate that adolescents with borderline hypertension displaying these characteristics have a greater risk for EH than previously reported.

Adolescent↗

PubMedDate not supplied

Effect of salt loading on the cardiovascular response to stress in adolescents.

This study investigated, in normotensive adolescents, three accepted risk factors for essential hypertension (EH): stress, dietary salt, and parental history (genetic risk). The cardiovascular response to mental stress was evaluated before and after salt loading in eight subjects without, and in seven with, a family history (FH) of EH. The effect of salt loading on the FH positive group was to increase significantly the stress-induced systolic and diastolic pressure while the heart rate response decreased. Salt loading resulted in no change in cardiovascular response to stress in the FH negative group.

Adolescent↗

PubMedDate not supplied