A group of 10 borderline hypertensive obese subjects had higher (P less than 0.05) supine plasma norepinephrine (NE), epinephrine, and PRA levels as well as greater (P less than 0.05) NE responses to upright posture and isometric handgrip exercise than 12 nonobese controls. Plasma NE as well as mean arterial pressure (MAP) responses to posture and handgrip in the obese patients demonstrated a significant decrement at week 2 after the onset of a low calorie diet. Decrements in plasma NE and MAP responses to posture were correlated (r = 0.61; P less than 0.05) throughout an 8-week period of weight loss in these borderline hypertensive obese subjects. In 15 normotensive obese subjects as well as in the 10 borderline hypertensive obese subjects, weight reduction associated with a very low calorie intake was accompanied by a reduction in supine plasma NE, epinephrine, and MAP 2 weeks after the onset of dieting. PRA decreased after 8 weeks of dieting in both obese groups, and these PRA decrements were correlated with reductions in MAP and decrements in plasma NE. We conclude that enhanced sympathetic activity may play a role in the maintenance of elevated blood pressure in obese individuals. Decreases in PRA and blood pressure associated with weight loss in both normotensive and hypertensive obese individuals occurs, in part, secondary to reductions in plasma NE levels.

This study examines the influence of dopamine on catecholamine and aldosterone secretion in normotensive individuals. The responses of plasma aldosterone (PA), norepinephrine (NE), and PRA to upright posture and isometric handgrip were studied in five normal males on a constant 50-meq Na intake before and after 4 days of administration of the dopamine agonist, bromergocriptine (BEC; 2.5 mg three times a day). In addition, the PA responses to graded angiotensin II and ACTH infusions were examined before and during BEC. Supine PA and PRA were not altered by BEC, but basal NE was reduced significantly (P < 0.01) from 204 +/- 29 to 98 +/- 12 pg/ml after BEC. There was an accompanying significant reduction in upright mean arterial pressure during BEC administration. The PA and NE during upright posture and isometric handgrip were significantly suppressed by BEC, but PRA responses were unaltered. BEC produced a significiant (P < 0.025) suppression of the PA response to graded angiotensin II infusions but did not alter the PA response to graded ACTH. Our findings indicate that in normal man there is a pronounced inhibitory effect of dopaminergic pathways on catecholamine scretion and regulation of upright mean arterial pressure. Results of the posture study would suggest that dopamine-mediated PA alterations occur independently of changes in the levels of PRA. The finding that BEC suppressed PA responses to angiotensin II and posture but not to ACTH would imply that dopamine selectively exerts its effect or adrenal angiotensin II-mediated aldosterone secretion.

The effect of weight reduction on levels of upright plasma norepinephrine (NE) and epinephrine (E) was studied in 20 obese patients maintained on a hypocaloric protein diet. Subjects were divided into 2 groups on either a constant 120 (N=13) or 40 (N=7) mmole sodium intake. Initial upright NE levels were higher (P < 0.001) in obese subjects (610 \ m=+-\ 52 pg/ml) than in non-obese controls (325 \m=+-\25 pg/ml). Initial NE in obese subjects correlated (r=0.6, P < 0.01) with mean arterial pressure. Weight loss in both sodium intake groups was accompanied by a progressive decline in upright NE and by 8 weeks levels were decreased in all study subjects by a mean of 42 per cent (P < 0.01) from baseline. Reductions in upright E from baseline were not as pronounced but were significant (P < 0.05) at 8 weeks on both sodium intakes. We have previously shown that mean arterial pressure and PRA decrease significantly in obese subjects during supplemented fasting independent of sodium intake. In the present study reductions in body weight correlated (r=58, P < 0.05) with both the fall in NE levels at 8 weeks (r=0.5, P < 0.05) and with reduction in upright PRA (r=0.49, P < 0.05) at weeks 4 to 8. Changes in upright E did not correlate with weight and blood pressure reductions. We conclude that reduction in caloric intake in obese patients is accompanied by significant reductions in upright NE and E that may contribute to the decline in resting blood pressure. The decrease in upright PRA with weight loss could result from depression in sympathetic nervous system activity.

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1. To investigate factors regulating blood pressure in obesity we have compared Na+ transport mechanisms and plasma noradrenaline (NA) responses to upright posture and isometric hand grip exercise in obese patients with transport mechanisms and NA responses in age, sex and race matched non-obese subjects. In the obese subjects we examined the effects of caloric restriction and weight reduction over a 12 week period on intracellular erythrocyte cation concentrations, Na+,K+-dependent ATPase activity and 86Rb uptake as well as responses of NA, plasma renin activity (PRA), aldosterone and mean arterial pressure to posture and isometric exercise. 2. Obese patients had greater (P < 0.05) basal supine plasma NA as well as enhanced NA responses to upright posture and exercise. Supine plasma NA as well as NA responses were reduced (P < 0.05) after 4 weeks caloric restriction and PRA and aldosterone responses were decreased (P < 0.05) after 8 weeks caloric restriction. Plasma NA at the onset of the diet correlated (r = 0.68, P < 0.01) with blood pressure, and decrements in NA and blood pressure were also related (r = 0.60, P < 0.01). Reductions in supine PRA and supine plasma NA during wieght loss were correlated (r = 0.55, P < 0.05) and the reduction in PRA may therefore be secondary to a decrease in sympathetic nervous system activity. 3. The intracellular Na+/K+ ratio in erythrocytes was greater in the obese patients than in non-obese controls whereas erythrocyte Na+,K+-ATPase activity and 86Rb uptake in obese patients was reduced (P < 0.01). There were significant negative correlations between Na+,K+-ATPase activity and 86Rb uptake and the degree of obesity. Although Na+,K+-ATPase and 86Rb increased and intracellular Na+ decreased during the 12 weeks of weight loss, they remained altered compared with values in non-obese subjects.