The effectiveness of behavioral methods in lowering blood pressure was evaluated against anti-hypertensive drug treatment. Patients with mild hypertension were studied twice a week for 8 weeks under one of the four following conditions: blood pressure biofeedback, Benson's relaxation response, drug treatment, and a control procedure consisting of the home self-monitoring of blood pressure. The groups were composed of nine patients each, primarily males between the ages of 35 and 60 years. Extensive baseline, treatment, and follow-up assessments were obtained of home blood pressure recordings and psychophysiological variables in the laboratory (heart rate, blood pressure, skin conductance, breathing rate, and frontalis muscle tension). Drug treatment was found to be markedly superior to all of the behavioral procedures in the regulation of blood pressure in the home recordings. With regard to laboratory measures of blood pressure, biofeedback was as effective as drugs and more effective than relaxation or the selfmonitoring control procedure in lowering diastolic but not systolic blood pressure. In addition, neither the relaxation response nor the control procedure had any effect on the regulation of blood pressure.

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Plasma renin substrate, a widely measured parameter of the renin reaction, is quantitated indirectly by the measurement of liberated angiotensin I upon exhaustive incubation of plasma with added renin. To overcome methodological problems of this assay system, we have developed a direct radioimmunoassay for this plasma protein using renin substrate purified from pooled plasma of normotensive subjects as the antigen. Comparison of substrate quantitated by the two assay systems (direct and indirect) indicates a 1:1 correlation with the exception of certain subjects with elevated substrate levels induced by estrogen therapy. To study the possibility of multiple substrate forms, we have made a comparison of substrate quantitated by both radioimmunoassays in conjunction with electrophoresis of plasma on polyacrylamide gel. One major form of substrate with a retardation factor (Rf) = 0.60 was found in normotensive and essential hypertensive subjects which gave a 1:1 correspondence on quantitation by the two methods. In contrast, six of 16 women on oral contraceptives demonstrated three forms of substrate (Rf = 0.16, 0.35, and 0.60) on electrophoresis. Substrate with Rf = 0.16 and 0.35 did not cross-react with the antiserum prepared against substrate from normotensive subjects, implying structural differences in these proteins.

The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.

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