SUMMARY Systemic, renal and splanchnic hemodynamics, intravascular volume, circulating catecholamine levels and plasma renin activity were compared in 39 patients with borderline hypertension and 28 normotensive subjects, who were less than 5% (n = 42, lean patients) or more than 40% overweight (n = 25, obese patients). Lean borderline hypertensive patients had greater cardiac output (p < 0.05), heart rate (p < 0.01) and renal blood flow (p < 0.05); cardiopulmonary redistribution of intravascular volume (p < 0.05); and higher circulating norepinephrine levels (p < 0.05). Obese normotensive subjects also showed an increased cardiac output (p < 0.005), stroke volume (p < 0.01), left ventricular stroke work (p < 0.05), and renal blood flow (p < 0.05) (but not respective indexes), but intravascular volume was expanded (p < 0.05) without redistribution and circulating catecholamine levels were normal. Obese borderline hypertensive patients had hemodynamic characteristics similar to those of obese normotensive subjects except for an increased peripheral resistance (p < 0.05). The data indicate that although both populations have an increased cardiac output, the lean borderline hypertensive patients have signs of enhanced adrenergic activity as evidenced by higher circulating catecholamine levels and heart rate with blood volume translocation to the cardiopulmonary circulation. In contrast, the obese subjects (whether normotensive or borderline hypertensive), who also have increased cardiac output, seem to have normal adrenergic activity and an expanded intravascular volume without cardiopulmonary redistribution.YOUNG PATIENTS with borderline blood pressure values are at least three times more likely to develop established essential hypertension as age-matched normotensive subjects.'1 2 Elevated resting cardiac output and heart rate have been identified as predictors for the development of essential hypertension into a state with more persistently elevated arterial pressure and periph-

In rats, gonadal steroid hormones present during the neonatal period produce permanent or "organizational" effects that play a role in the sexual differentiation of the brain and sexually dimorphic patterns of behavior. Because there exists a sexually dimorphic pattern in the development of hypertension in the spontaneously hypertensive rat (SHR), we examined the influence of neonatal gonadal hormones on arterial pressure and body weight in these rats. Male SHR rats were castrated or sham-operated (controls) on their day of birth. Female rats received 1.25 mg testosterone propionate (TP) or sesame oil vehicle on their 2nd day of life. Sham-operated males and TP and oil females were gonadectomized at 81 days of age. To examine the transient or "activational" effects of gonadal steroid hormones, testosterone implants were placed subcutaneously in all rats at 128 days of age and were removed at 170 days of age. The rats were killed at 202 days of age, and selected organ weights were determined. During the original treatment, days 44-79, blood pressure in castrated males was comparable to that of control females, whereas blood pressure in neonatal TP females was not different from that of control males. When exposed to testosterone in adulthood, blood pressure increased more in neonatal TP female rats than in control females. Partial correlation analysis indicated that differences in body weights among the groups could not account for their variances in blood pressure. These data suggest that the neonatal gonadal hormone milieu contributes significantly to the sexually dimorphic pattern of hypertension development in the SHR.

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Extracts of atrial and ventricular rat heart tissue were prepared in phosphatebuffered saline and boiled (PBS-boiled) or in acetic acid and fractionated using Sephadex G-75. The extracts were injected intravenously into anesthetized nondiuretic (i.e., not hydrated) rats to assay for natriuretic activity. PBS-boiled atrial extract caused urinary sodium excretion (UNaV) to increase significantly (P < 0.05) by 672 5 307% (+SE) during the 10 min after injection; whereas no significant change in U,,V occurred after injection of PBS alone or ventricular extract. UKV and urine volume increased significantly by 400 + 236% and 499 5 105%, respectively, after injection of PBS-boiled atrial extract. Pooled active fractions from Sephadex (3-75 of acid atrial extract (lyophilized and reconstituted in PBS) caused UNaV and urine volume to increase significantly by 1015 5 401% and 807 + 291%, respectively, and a smaller but significant increase in UKV of 158 5 23%. The natriuretic activity of acid atrial extract eluted in the molecular weight range of 3600 to 44,OOO daltons, was unaffected by heating in a boiling water bath, treatment with concanavalin A, incubation with plasma, or removing the head of the assay rat, but was abolished by treatment with trypsin. These properties do not generally resemble those of the natriuretic factors in blood and urine previously reported by others. 502

Atrial natriuretic factor (ANF) causes plasma fluid to shift out of the circulation and enhances the escape of radiolabeled albumin. Examination of the mechanisms by which ANF alters microcirculatory fluid and protein transfer will likely require studies in localized vascular regions. This study was aimed at determining the specific organs in which ANF increases the escape of albumin. Anesthetized, splenectomized rats that had both kidneys removed were infused with vehicle alone or rat ANF-(99-126) at 0.025, 0.05, 0.1, or 0.5 micrograms.min-1.kg-1 for 2 hours (n = 8 per group). Total red cell and plasma volumes were measured with chromium-51-labeled erythrocytes and iodine-125-labeled albumin, respectively. At the end of 2 hours, the rats were frozen in liquid nitrogen, and organ blood volumes and tissue 125I-albumin were determined. ANF decreased plasma volume at infusion rates of 0.1 and 0.5 micrograms.min-1.kg-1. ANF increased the rate at which 125I-albumin escaped from the overall circulation at infusion rates of 0.1 and 0.5 micrograms.min-1.kg-1. At an ANF infusion rate of 0.1 micrograms.min-1.kg-1, the albumin escape rate increased in the gastrointestinal tract, skeletal muscle, heart, and lungs. At an infusion rate of 0.5 micrograms.min-1.kg-1, the albumin escape rate increased in the gastrointestinal tract, muscle, and skin, but not the lungs. These findings suggest that at pathophysiological levels, ANF shifts protein out of the circulation in peripheral vascular beds and the lungs and may contribute to pulmonary edema in states such as congestive heart failure. At pharmacological levels, ANF may be protective of the lungs by preventing increased pulmonary albumin escape.