We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)

In male rats, bilateral adrenalectomy leads to an increase in circulating ACTH that persists for 2 hr, followed by a decline to control levels which persist from the 6th to approximately the 48th hr after operation. Thereafter, circulating ACTH increases to high levels. No such triphasic response is seen after sham adrenalectomy, the only increase being a brief elevation 2.5 min after the stress. This increased ACTH secretion after bilateral adrenalectomy is promptly inhibited by corticosterone replacement, although it is not completely prevented. One and 2 hr after adrenalectomy the increase in circulating ACTH produced by laparotomy stress is much greater than it is in sham adrenalectomized control animals, but by 24 hr the response has returned to normal. The hyperresponsiveness to laparotomy following adrenalectomy is prevented if the rats receive corticosterone injections 120 and 60 min before the stress. The data suggest that there is a rapid inhibition of ACTH secretion produced by corticosterone secreted from the rat adrenal in response to stress. {Endocrinology 91: 961, 1972). S INCE most investigators have not ob-served an increase in plasma ACTH until 48 hr or more after adrenalectomy, it has been argued that the ACTH response to a decline in circulating corticosteroids is slow (1). However, there is evidence suggesting that ACTH secretion is inhibited within minutes after the start of a corticosteroid infusion (2-6), and there are very few reports of ACTH measurements during the first 4 hr after adrenalectomy. Changes in pituitary morphology (7) and pituitary ACTH content (8,9) after bilateral adrenalectomy in rats are consistent with increased ACTH secretion during this period. Therefore we have studied in detail the effects on circulating ACTH of bilateral adrenalectomy, with particular emphasis on the first 2 hr after adrenalectomy. Portions of the results have previously been reported in an abstract (10).

To test whether there is a circadian rhythm in the ACTH response to stress, young female rats were exposed to a variety of ACTH-releasing stimuli at 0600 and 1800 h and changes in circulating ACTH and corticosterone were measured. The results of these experiments suggested that after the high intensity stimuli of laparotomy with intestinal traction or 250 mug histamine ip/100 g BW, the morning ACTH response was greater than the evening response. However, the ACTH response to ip saline was greater in the evening in one experiment and greater in the morning in a second experiment. Plasma corticosterone responses were faster and greater in the morning in the first experiment and in the evening in the second experiment. The ACTH response to 125 mug histamine ip/100 g BW was greater in the evening and the change in corticosterone was greater in the morning. Thus, after low intensity stimuli, the ACTH responses appeared to depend on both the lag time prior to the corticosterone response, and its magnitude. To test this possibility, rats were adrenalectomized and the ACTH response was measured 7.5 and 15 min after the start of surgery and after injection with either 2% EtOH-saline, or 50 mug corticosterone at operation, or with 30 mug corticosterone at 5 min. Compared with ACTH levels in rats treated with vehicle, ACTH levels were decreased 7.5 min after 50 mug corticosterone at operation (P less than 0.01), but not after 30 mug corticosterone at 5 min. ACTH levels were slightly reduced 10 min after 30 mug corticosterone at 5 min compared with those of rats injected with vehicle at operation (P less than 0.05). These results are consistent with the interpretation that corticosterone secretion modifies stress-induced ACTH secretion via the fast-feedback effect. Comparison of the ACTH responses to acute adrenalectomy plus injection with EtOH-saline at 0600 and 1800 h demonstrated that, in the absence of a corticosterone response to the stress, the ACTH response is greater in the morning that in the evening (P less than 0.01). Finally, this group of experiments suggests strongly that the responsivenss of rat adrenal glands to ACTH increases markedly between 0600 and 1800 h.