Hemodynamic patterns and duration of post-dynamic exercise hypotension in hypertensive humans.

We investigated: 1) the mechanism of the hypotensive effect of a single bout of dynamic exercise in hypertensive subjects by measuring hemodynamic parameters before and for 2 h after treadmill exercise, and 2) the duration of the effect using ambulatory blood pressure (BP) monitoring once the subjects left the test site. Ten minutes after exercise there was a significant decrease from baseline systolic pressure (SP; -14 +/- 3 mm Hg), mean arterial pressure (MAP; -7 +/- 2 mm Hg), total peripheral resistance (TPR; -3.7 +/- 1.2 units), calf vascular resistance (CVR; -25.4 +/- 4.1 units), and an increase in HR (19 +/- 2 bpm). The changes in SP, DP, MAP, and HR were maintained during the 2 h of post-exercise monitoring; CVR remained decreased for 1 h; TPR returned to baseline within 20 min and then tended to be slightly elevated. CO was significantly decreased at 50, 60, and 120 min after exercise. We conclude that the early decline in BP after dynamic exercise in hypertensive subjects follows a biphasic pattern: 1) an initial decrease in total and regional vascular resistance with maintained CO, 2) followed by increasing resistance and decrease CO. Pre-exercise hypertensive BP values returned during subsequent ambulatory monitoring.

Squatting revisited: comparison of haemodynamic responses in normal individuals and heart transplantation recipients.

BACKGROUND: Squatting produces a prompt increase in cardiac output and arterial blood pressure which is accompanied by an immediate decrease in heart rate and forearm vascular resistance. The rise in cardiac output and blood pressure has been attributed to augmented venous return from compression of leg veins, while the decreases in heart rate and forearm vascular resistance are probably due to activation of cardiopulmonary and arterial baroreflexes. Haemodynamic patterns in nine normal men and six heart transplant recipients during 2 min of squatting were examined to determine the role of cardiac innervation in the mediation of these responses. METHODS: Stroke volume was monitored by ensemble averaged thoracic impedance cardiography and blood pressure was determined with an Ohmeda fingertip plethysmograph. These techniques provided continuous measurements which were capable of detecting transient and non-steady state changes. Forearm blood flow was measured with venous occlusion plethysmography. Measurements were obtained after 3 min of quiet standing, immediately after squatting, and at 20, 60, and 120 s of sustained squatting. RESULTS: Both groups exhibited similar increases in stroke volume index (normal individuals 10.5 ml/m2; heart transplant recipients 10.3 ml/m2) and mean arterial pressure (normal individuals 8.5 mm Hg; heart transplant recipients 5.0 mm Hg) which were sustained throughout squatting. Each group also showed an initial decrease in peripheral resistance (normal individuals 3.6 units; heart transplant recipients 7.7 units) followed by a return to baseline values after 20 s. Heart rate decreased in normal individuals (10 beats/min) but was unchanged or minimally increased (2 beats/min) in heart transplant recipients. Forearm vascular resistance was conspicuously decreased in normal individuals (47.8 units) but only minimally (20.9 units) and not significantly in heart transplant recipients. CONCLUSIONS: The major haemodynamic responses to squatting (increased cardiac output and blood pressure) are similar in normal individuals and heart transplant recipients. These responses are primarily due to augmented venous return and are not altered by cardiac denervation. Both groups also exhibited a transient decline in peripheral vascular resistance which is most likely mediated by arterial baroreflexes activated by the acute rise in arterial blood pressure. The absence of a significant decrease in forearm vascular resistance in heart transplant recipients suggests that this response is partially mediated by cardiopulmonary or ventricular baroreflexes or that local forearm flow mediated vasodilatation remains impaired after heart transplantation.

Comparison of arterial occlusion and ischaemic exercise for the study of vasodilatation in the human calf.

1. Calf blood flow was measured by venous occlusion plethysmography to compare two stimuli for eliciting maximal calf vascular conductance: (i) 10 min of arterial occlusion and (ii) isolated exhaustive calf exercise with ischaemic occlusion. The subjects were semi-supine with the calf in position for immediate blood flow measurements after release of the occluding cuff. Three groups of subjects were studied: young [35 years (SD 9, n = 9)], old [57 years (SD 5, n = 10)] and patients with congestive heart failure [63 years (SD 7, n = 7)]. 2. Occlusion and ischaemic exercise were equally effective in producing maximal calf vascular conductance in each of the subject groups. Maximal calf vascular conductance (ml min-1 100 ml-1 mmHg-1) was equivalent in the young [ischaemic exercise 0.54 (SEM 0.03), occlusion 0.54 (SEM 0.05)] and old [ischaemic exercise 0.47 (SEM 0.05), occlusion 0.48 (SEM 0.04)] subjects. However, patients with congestive heart failure exhibited significantly reduced maximal calf vascular conductance [ischaemic exercise 0.20 (SEM 0.02), occlusion 0.20 (SEM 0.01)]. 3. Analysis of the curves, generated by plotting serial calf vascular conductance values obtained immediately and every 15 s after occlusion cuff release for 165 s, revealed differences in the pattern of vasodilatation after occlusion and ischaemic exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adding beta-2 agonism does not improve beta-1 blockade exercise responses in hypertensives.

We tested the hypothesis that celiprolol, a beta-1 adrenoceptor antagonist with the ancillary property of beta-2-mediated vasodilation, would increase blood flow to active muscles during exercise and result in less impairment of exercise performance compared with the beta-1 antagonist atenolol. After an initial 3-wk washout phase, 11 untrained hypertensive men participated in a 6-wk crossover study of the two drugs. Each treatment phase was followed by a 3-wk placebo phase. Resting forearm and calf vascular resistance measured by venous occlusion plethysmography and submaximal and maximal bicycle ergometry exercise responses were evaluated at the end of each treatment and placebo phase. Celiprolol significantly decreased resting forearm and calf vascular resistance whereas atenolol had no significant effect. Neither beta-blocker significantly affected submaximal exercise oxygen uptake, rate of perceived exertion, minute ventilation, or respiratory exchange ratio. Both beta-blockers significantly and similarly decreased peak oxygen uptake; celiprolol 23.9 +/- 1.7, atenolol 24.9 +/- 1.7, placebo 27.3 +/- 1.3 ml.kg-1.min-1. Our findings suggest that during exercise while on beta-blockade, other factors such as sympathetic vasoconstriction or local metabolic vasodilation may override beta-2-mediated vasodilation. Thus, the addition of beta-2 agonism to beta-1 antagonism decreases resting vascular resistance but offers no advantage over conventional beta-1 blockade therapy during exercise.

Elevated free cortisol index in pregnancy: possible regulatory mechanisms.

Biologically active plasma free cortisol increases markedly in pregnancy. In this investigation the free cortisol index (FFI) in the plasma of pregnant and nonpregnant women was measured by a charcoal adsorption technique. The circadian FFI patterns were virtually identical in the two groups, but in gravid women there was a substantial and sustained elevation of the FFI. Sequential studies during gestation and post partum revealed increasing responsiveness of the maternal adrenal glands to adrenocorticotropic hormone (ACTH) and decreasing suppressibility of the FFI by dexamethasone as pregnancy advanced. Persistence of normal circadian rhythmicity in spite of a continuously elevated FFI and resistance to dexamethasone suppression suggest control of cortisol secretion by normal regulatory mechanisms in pregnancy with resetting of the maternal feedback mechanisms to higher levels. This resetting and the lack of manifestations of cortisol excess in pregnancy might result from tissue refractoriness to cortisol. Elevated free cortisol would be needed to maintain homeostasis. The necessary increase in the production of cortisol could be facilitated by an enhanced responsiveness of the maternal adrenal glands to ACTH.

Desoxycorticosterone in normal pregnancy. III. Evidence of a fetal source of desoxycorticosterone.

The source of the markedly increased secretion of desoxycorticosterone (DOC) in pregnancy has not been precisely defined. Earlier studies indicated that elevated DOC does not arise from the maternal adrenal glands. The previously observed steep gradient between fetal and maternal DOC and DOC sulfate concentrations seemed to point to a fetal source. A recent study suggests that Doc may also be derived from extra-adrenal conversion of maternal progesterone. The present investigation documents a lack of synchrony between maternal diurnal plasma cortisol and DOC patterns. Not only were the previous observations of steep gradients of DOC and DOC sulfate between fetal and maternal circulations confirmed, but also the finding of extremely high urinary excretion of DOC sulfate indicated that the sulfurylated steroid passes across the placenta. A direct linear correlation was noticed between cortisol and DOC in amniotic fluid. These observations suggest that the increased DOC arises from within the fetoplacental unit but do not rule out a maternal source.

Desoxycorticosterone in normal pregnancy. II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone.

Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.