Clin. Invest. 1992.90:1707-1712

Quantitative autoradiography revealed large numbers of angiotensin-II (AT) receptors in the 18-day-old rat embryo. The selective AT-1 antagonist DuP 753 readily competed for AT receptors in liver, lung parenchyma, and choroid plexus, and these receptors are classified as AT-1 receptors. The selective AT-2 displacers CGP 42112 A and/or PD 123177 competed with high affinity with AT bound to most receptors located in skeletal muscle, skin, diaphragm, bronchi, and stomach, and these receptors are classified as AT-2 receptors. The amount of AT-2 receptors in fetal tissue was more than 10-fold higher than that of AT-1 receptors. In skeletal muscle and skin, DuP 753 competed with AT in the presence of 10(-7) M CGP 42112 A, indicating the presence of small numbers of AT-1 receptors. In liver and lung parenchyma, binding to AT-1 receptors was sensitive to guanine nucleotides. AT binding to AT-2 receptors in fetal skin and skeletal muscle was insensitive to guanine nucleotides. AT stimulated phosphoinositide hydrolysis in liver (ED50, 64 nM) and in skin and skeletal muscle (ED50, 62 nM); this was inhibited by DuP 753 (liver IC50, 38 nM; skin and skeletal muscle IC50, 26 nM), but not by PD 123177 in concentrations up to the micromolar range. AT-1 receptors are probably coupled to G-proteins, and their stimulation increases phosphoinositide hydrolysis. AT-2 receptors may not be linked to G-proteins, their stimulation is not associated with phosphoinositide hydrolysis, and the nature of their second messenger system(s) is presently unknown.

No abstract

Six healthy volunteers received 15 mg midazolam, 50 mg ephedrine, or placebo orally before a 50-minute aerobic treadmill exercise and in a control session. Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake. Heart rate, blood pressure, critical flicker fusion test, Maddox wing test, and visual analog scales relating to mood and feelings of tiredness were included in the sessions as pharmacodynamic measures. These tests were made at 35, 55, and 75 minutes and at 2, 2 1/2, 3 1/2, and 5 hours after drug intake. Exercise impaired the absorption of midazolam and counteracted the midazolam-induced decrement in flicker fusion threshold. Whether the effect on flicker fusion was caused mainly by the pharmacokinetic changes or by a general alerting effect of exercise cannot be verified by this experiment. The kinetics of ephedrine was not affected by exercise, but exercise enhanced the tachycardic response to ephedrine and abolished its pressor effect.