Hemodynamic response to converting enzyme inhibition at rest and exercise in humans

The response of the systemic circulation to acute inhibition of the converting enzyme with 25 mg of oral Captopril (Squibb) was studied in six normal sodium-replete male volunteers at rest and during exercise, together with its effects on exercise capacity for graded uninterrupted exercise. In recumbent subjects at rest Captopril did not affect arterial pressure or heart rate, and plasma renin activity rose 2.5-fold (P less than 0.05). In subjects in the sitting position, at rest and during exercise until exhaustion, Captopril reduced mean brachial intra-arterial pressure by an average of 7 Torr in comparison to placebo (P less than 0.001). Captopril's hypotensive effect was caused by a reduction of systemic vascular resistance (P less than 0.01), without changes of cardiac output (measured by CO2 rebreathing), heart rate, or stroke volume. Plasma renin activity was significantly higher during Captopril (P less than 0.001). Peak oxygen uptake and exercise duration were the same after administration of Captopril or placebo. The data demonstrate that the renin-angiotensin system is not involved in the homeostasis of blood pressure in supine sodium-replete humans, but has a modest role in blood pressure regulation when posture is changed from supine to upright. The orthostatic effect of Captopril is maintained during upright exercise. Furthermore the reduction of systemic vascular resistance by Captopril does not affect peak oxygen uptake.     

Beta-adrenoceptors and the regulation of blood pressure and plasma renin during exercise

The relative role of beta 1- and beta 2-adrenoceptors in the regulation of blood pressure and plasma renin at rest and during exercise was studied in 17 normal male volunteers. They performed, in a randomized order and according to a double-blind crossover study design, three graded and uninterrupted exercise tests until exhaustion after being pretreated during 3 consecutive days with a placebo, with a predominantly beta 1-blocker (atenolol, 50 mg once/day), or with a predominantly beta 2-blocker (ICI 118551, 20 mg 3 times/day). Both drugs caused a decrease of heart rate, but the reduction by ICI 118551 was less pronounced at rest and no additional decline occurred at exercise. ICI 118551 did not affect blood pressure at rest, but during exercise diastolic blood pressure was higher than after a placebo. Atenolol lowered systolic blood pressure at rest and suppressed the exercise-induced increase in systolic blood pressure. At rest and during exercise plasma renin activity was lowered by predominantly beta 1-blockade and unchanged during beta 2-antagonism. The exercise-induced increase in plasma renin was, however, not affected by the beta 1-blocker. After atenolol the urinary excretion of aldosterone was decreased but the plasma aldosterone concentration was not changed. ICI 118551 did not alter plasma or urinary aldosterone. Our results therefore provide further evidence that the adrenoceptors mediating the release of renin at rest and during exercise in humans are partially of the beta 1-subtype, whereas beta 2-adrenergic receptors probably play only a minor role in the control of renin secretion, especially at exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

A method for calculation of human systolic and diastolic blood pressures using an elastic reservoir theory of the systemic arterial system,and some clinical and physiological applications

Two equations have been developed that describe the interrelationship of the clinically measurable variables of the human systemic arterial system. An approximation method is given for their simultaneous solution for systolic and diastolic pressures in terms of heart rate, cardiac output, total peripheral resistance, and aortic distensibility. In this way, blood pressures were calculated for various clinically important and didactically useful situations. The effects on systolic and diastolic pressures due to changing either cardiac output or peripheral resistance or heart rate or aortic distensibility alone are shown. The effects on pulse pressure of varying cardiac output and peripheral resistance while holding mean arterial pressure constant are demonstrated. Compensatory mechanisms in hypertension and exercise are explored. Opinions and conclusions contained in this report are those of the author. They are not to be construed as necessarily reflecting the views or the endorsement of the Navy Department.     

The effect of naloxone on blood pressure, heart rate, plasma catecholamines, renin activity and aldosterone following exercise in healthy males

There is evidence that endogenous opioids are involved in blood pressure regulation. In the present study the effect of naloxone on the cardiovascular, sympathoadrenomedullary and renin-aldosterone response to physical exercise was investigated in 8 healthy males. Each subject performed a submaximal work test twice, i.e. with and without naloxone. The test consisted of ergometer bicycling for 10 minutes on 50% of the maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC. Ten minutes before exercise the subjects received in a single blind randomized order a bolus dose of naloxone (100 micrograms/kg) or a corresponding volume of the preservatives of the naloxone preparation (control) followed by a slow infusion of naloxone (50 micrograms/kg/h) or preservatives, respectively. Naloxone was without effect on the exercise-induced changes in systolic blood pressure, heart rate, plasma noradrenaline, renin activity and aldosterone, but the adrenaline response increased markedly. The present results indicate that opioid receptors are involved in the plasma adrenaline response to submaximal exercise, but not in the regulation of systolic blood pressure, heart rate, plasma noradrenaline, renin activity and plasma aldosterone.     

Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurohumoral and cardiopulmonary response to sustained submaximal exercise in the dog

Neurohumoral, cardiovascular, and respiratory parameters were evaluated during sustained submaximal exercise (3.2 km/h, 15 degrees elevation) in normal adult mongrel dogs. At the level of activity achieved (fivefold elevation of total body O2 consumption and threefold elevation of cardiac output), significant (P less than 0.05) increases in plasma norepinephrine and epinephrine concentration (from 150 +/- 23 to 341 +/- 35 and from 127 +/- 27 to 222 +/- 31 pg/ml, respectively) were present, as well as smaller but significant increases in plasma renin activity and plasma aldosterone concentration (from 2.2 +/- 0.3 to 3.1 +/- 0.6 ng X ml-1 X h-1 and from 98 +/- 8 to 130 +/- 6 pg/ml, respectively). Plasma arginine vasopressin increased variably and insignificantly. The cardiovascular response (heart rate, systemic arterial and pulmonary arterial pressures, left ventricular filling pressure, and calculated total peripheral and pulmonary arteriolar resistance) closely paralleled that of human subjects. Increased hemoglobin concentration was induced by exercise in the dogs. The ventilatory response of the animals was characterized by respiratory alkalosis. These data suggest similarities between canine and human subjects in norepinephrine, plasma renin activity, and plasma aldosterone responses to submaximal exercise. Apparent species differences during submaximal exertion include greater alterations of plasma epinephrine concentration and a respiratory alkalosis in dogs.     

Cardiovascular adjustments to rhythmic handgrip exercise: relationship to electromyographic activity and post-exercise hyperemia

The purpose of this study was to examine the association among electromyographic (EMG) activity, recovery blood flow, and the magnitude of the autonomic adjustments to rhythmic exercise in humans. To accomplish this, 10 healthy subjects (aged 23-37 y) performed rhythmic handgrip exercise for 2 min at 5, 15, 25, 40, and 60% of maximal voluntary force. Heart rate and arterial blood pressure were measured at rest (control), during each level of exercise, and for 2 min following exercise (recovery). The rectified, filtered EMG activity of the exercising forearm was measured continuously during each level of exercise and was used as an index of the level of central command. Post-exercise hyperemia was calculated as the difference between the control and the average recovery (2 min) forearm blood flows (venous occlusion plethysmography) and was examined as a possible index of the stimulus for muscle chemoreflex activation. Heart rate, arterial pressure, forearm EMG activity, and post-exercise hyperemia all increased progressively with increasing exercise intensity. The magnitudes of the increases in heart rate and arterial pressure from control to exercise were directly related to both the level of EMG activity and the degree of post-exercise hyperemia across the five exercise intensities (delta heart rate vs EMG activity: r = 0.99; delta arterial pressure vs EMG activity: r = 0.99; delta heart rate vs hyperemia: r = 0.99; and delta arterial pressure vs hyperemia: r = 0.98; all p less than 0.01). Furthermore, the level of EMG activity was directly related (r = 0.99) to the corresponding degree of hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular responses to military antishock trouser inflation during standing arm exercise

Military antishock trousers (MAST) inflated to 50 mmHg were used with 12 healthy males (mean age 28 +/- 1 yr) to determine the effects of lower-body positive pressure on cardiac output (Q), stroke volume (SV), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), total peripheral resistance (TPR), and O2 uptake (VO2) during graded arm-cranking exercise. Subjects were studied while standing at rest and at 25, 50, and 75% of maximal arm-cranking VO2. At each level, rest or work was continued for 6 min with MAST inflated and for 6 min with MAST deflated. Order of inflation and deflation was alternated at each experimental rest or exercise level. Measurements were obtained during the last 2 min at each level. Repeated-measures analysis of variance revealed significant increases (P less than 0.001) in Q, SV, and MABP and a consistent decrease in HR with MAST inflation. There was no apparent change in Q/VO2 between inflated and control conditions. There was no effect of MAST inflation on VO2 or TPR. MAST inflation counteracts the gravitational effect of venous return in upright exercise, restoring central blood volume and thereby increasing Q and MABP from control. HR is decreased consequent to increased MABP through arterial baroreflexes. The associated decrease in TPR is not observed, being offset by the mechanical compression of leg vasculature with MAST inflation.     

Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.     

Increases in intramuscular pressure raise arterial blood pressure during dynamic exercise.

This investigation was designed to determine the role of intramuscular pressure-sensitive mechanoreceptors and chemically sensitive metaboreceptors in affecting the blood pressure response to dynamic exercise in humans. Sixteen subjects performed incremental (20 W/min) cycle exercise to fatigue under four conditions: control, exercise with thigh cuff occlusion of 90 Torr (Cuff occlusion), exercise with lower body positive pressure (LBPP) of 45 Torr, and a combination of thigh cuff occlusion and LBPP (combination). Indexes of central command (heart rate, oxygen uptake, ratings of perceived exertion, and electromyographic activity), cardiac output, stroke volume, and total peripheral resistance were not significantly different between the four conditions. Mechanical stimulation during LBPP and combination conditions resulted in significant elevations in intramuscular pressure and mean arterial pressure from control at rest and throughout the incremental exercise protocol (P < 0.05). Conversely, there existed no significant changes in mean arterial pressure when the metaboreflex was stimulated by cuff occlusion. These findings suggest that under normal conditions the mechanoreflex is tonically active and is the primary mediator of exercise pressor reflex-induced alterations in arterial blood pressure during submaximal dynamic exercise in humans.     

Hormonal and renal responses to converting enzyme inhibition during maximal exercise

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.     

Effects of brain renin-angiotensin on cardiovascular function and saline intake in awake dogs

Initial studies were undertaken to investigate the effects of prolonged administration of angiotensin II (AII), 1 micrograms twice daily, via the lateral ventricles to mongrel dogs on arterial blood pressure and to determine if sodium intake was essential for the development of hypertension. Increasing AII levels in the cerebrospinal fluid for a prolonged period of time produced a sustained hypertensive state only in those dogs in which the daily intake of sodium was increased. The hypertension appeared to be due to an increase in total peripheral resistance. Central administration of AII increased both fluid intake and urine output. In order to assess the hemodynamic effects of increasing endogenous brain AII, renin was injected in doses of 0.025, 0.05, 0.1 and 0.3 units (from porcine kidney) into the lateral ventricles of chronically instrumented awake dogs. Hemodynamic variables were recorded prior to and one and 2 h after the central administration of renin. Renin produced a dose-dependent increase in mean arterial pressure with no significant change in heart rate or carotid, coronary and renal blood flow velocities. Chronic intraventricular administration of renin, 0.15 units twice daily to awake instrumented dogs receiving saline as the drinking fluid, markedly increased the daily intake of saline and increased diastolic and systolic blood pressure without increasing heart rate or carotid, coronary or renal blood flow velocities. There appears to be a direct significant relationship between the increase in mean blood pressure due to the intraventricular administration of renin and the volume of saline consumed.     

Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects.

The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.     

Acute effects of resistance exercise on arterial compliance.

Decreased central arterial compliance is an emerging risk factor for cardiovascular disease. Resistance training is associated with reductions in the elastic properties of central arteries. Currently, it is not known whether this reduction is from one bout of resistance exercise or from an adaptation to multiple bouts of resistance training. Sixteen healthy sedentary or recreationally active adults (11 men and 5 women, age 27 +/- 1 yr) were studied under parallel experimental conditions on 2 separate days. The order of experiments was randomized between resistance exercise (9 resistance exercises at 75% of 1 repetition maximum) and sham control (seated rest in the exercise room). Baseline hemodynamic values were not different between the two experimental conditions. Carotid arterial compliance (via simultaneous B-mode ultrasound and applanation tonometry) decreased and beta-stiffness index increased (P < 0.01) immediately and 30 min after resistance exercise. Immediately after resistance exercise, carotid systolic blood pressure increased (P < 0.01), although no changes were observed in brachial systolic blood pressure at any time points. These measures returned to baseline values within 60 min after the completion of resistance exercise. No significant changes in these variables were observed during the sham control condition. These results indicate that one bout of resistance exercise acutely decreases central arterial compliance, but this effect is sustained for <60 min after the completion of resistance exercise.     

WISE 2005: stroke volume changes contribute to the pressor response during ischemic handgrip exercise in women.

The mechanism of the pressor response to small muscle mass (e.g., forearm) exercise and during metaboreflex activation may include elevations in cardiac output (Q) or total peripheral resistance (TPR). Increases in Q must be supported by reductions in visceral venous volume to sustain venous return as heart rate (HR) increases. Therefore, this study tested the hypothesis that increases in Q, supported by reductions in splanchnic volume (portal vein constriction), explain the pressor response during handgrip exercise and metaboreflex activation. Seventeen healthy women performed 2 min of static ischemic handgrip exercise and 2 min of postexercise circulatory occlusion (PECO) while HR, stroke volume and superficial femoral artery flow (Doppler), blood pressure (Finometer), portal vein diameter (ultrasound imaging), and muscle sympathetic nerve activity (MSNA; microneurography) were measured followed by the calculation of Q, TPR, and leg vascular resistance (LVR). Compared with baseline, mean arterial blood pressure (MAP) (P < 0.001) and Q (P < 0.001) both increased in each minute of exercise accompanied by a approximately 5% reduction in portal vein diameter (P < 0.05). MAP remained elevated during PECO, whereas Q decreased below exercise levels. MSNA was elevated above baseline during the second minute of exercise and through the PECO period (P < 0.05). Neither TPR nor LVR was changed from baseline during exercise and PECO. The data indicate that the majority of the blood pressure response to isometric handgrip exercise in women was due to mobilization of central blood volume and elevated stroke volume and Q rather than elevations in TVR or LVR resistance.     

Hormonal responses to exercise during moderate cold exposure in young vs. middle-age subjects.

The influence of moderate cold exposure on the hormonal responses of atrial natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30 degrees C) and cold (10 degrees C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10 degrees C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30 degrees C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30 degrees C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10 degrees C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30 degrees C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostaglandins modulate baroreflex-induced changes in blood pressure and myocardial function in anesthetized dogs

The purpose of our study was to investigate the role of prostaglandins in the changes in myocardial function and peripheral and coronary vascular resistance which accompany a generalized increase in sympathetic tone caused by carotid baroreflex unloading in the anesthetized dog. Bilateral carotid artery occlusion (BCO) with heart rate held constant by electrical pacing (150 beats/min) resulted in increases in systolic, (33%) diastolic (40%), and mean (35%) arterial pressures, LV systolic pressure (33%) and left ventricular (LV) dP/dt (37%). After blockade of prostaglandin synthesis with indomethacin (N = 11) or meclofenamate (N = 6) the increases in systolic (41%), diastolic (45%), and mean (41%) arterial pressures, LV systolic pressure (39%), LV dP/dt (52%), and cardiac work caused by BCO were significantly greater, in spite of the initially higher baseline values (11-18%) following the administration of the drugs. In contrast, the changes in circumflex coronary blood flow and coronary vascular resistance to BCO were essentially the same before and after inhibition of prostaglandin synthesis. Systemic prostaglandin synthesis may, therefore, play a significant role in the control of systemic arterial pressure and myocardial function, most probably by modulating the release of norepinephrine from adrenergic nerve terminals, without adversely affecting coronary blood flow regulation.     

Antihypertensive effect of total flavonoid fraction of Astragalus complanatus in hypertensive rats

The purpose of the present study was to quantify the antihypertensive effect of the total flavonoid (TF), extracted from the seed of Astragalus complanatus R. Brown, and to observe its effect on the renin-angiotensin system (RAS) in both renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). RHR were created by the two-kidney one clip (2K1C) method. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Plasma angiotensin II (AngII) and plasma renin activity (PRA) were measured with radioimmunoassay at 60 min after drug administration. The effects of TF on cardiac hemodynamics were also recorded in anesthetized RHR and SHR. TF was given by oral administration in low dose (100 mg/kg) and high dose (200 mg/kg) respectively. Compared to pre-administration control, TF induced an obvious decrease in systolic blood pressure in conscious normotensive Wistar rat, RHR and SHR. In the three groups the systolic blood pressure reached the lowest value at 60 min after TF. TF also induced a significant decrease in blood pressure in anesthetized RHR and SHR. At 60 min after treatment of TF, mean arterial pressure in high dose group (200 mg/kg) was decreased by 17% in RHR and by 17% in SHR respectively (P < 0.01). The depressor effect of TF lasted for at least 60 min. Cardiac output, heart rate and +/- dp/dtmax did not change. Conversely, total peripheral resistance was significantly decreased. The decrease in plasma AngII was found in both RHR and SHR. On the contrary, PRA increased at the same time. These findings suggested that TF is effective in reducing blood pressure in both RHR and SHR. The antihypertensive action of TF was attributed to a decrease in TPR secondary to a decrease in plasma concentration of AngII caused by TF.     

Effects of autonomic blockade on cardiac function at rest and during upright exercise in humans

The cardiac function was studied by radionuclide cardiography in eight healthy subjects at rest and during submaximal upright exercise before and after autonomic blockade with metoprolol and atropine. At rest the median stroke volume was reduced by 21% during autonomic blockade (P less than 0.01), but cardiac output was maintained by a concomitant increase in heart rate. The systolic blood pressure was reduced from 120 to 105 mmHg (P less than 0.01), and left ventricular ejection fraction was reduced from 61 to 56% (P less than 0.05). After autonomic blockade the heart rate reached during exercise was the same. Stroke volume and cardiac output were maintained through cardiac dilation. The increase in left ventricular end-diastolic volume was 31 vs. 10% during control conditions (P less than 0.01). The systolic blood pressure was reduced from 174 to 135 mmHg (P less than 0.01). Left ventricular ejection fraction was reduced from 75 to 67% (P less than 0.05), but the increase from rest to exercise was preserved. Total peripheral resistance was reduced by 17% (P less than 0.05). These findings suggest that the heart possesses intrinsic mechanisms to maintain cardiac output during submaximal upright exercise. End-diastolic dilation results in a preserved stroke volume despite a reduced contractility.     

Human cardiovascular and humoral responses to moderate muscle activation during dynamic exercise.

We examined the hypothesis that activation of the muscle metaboreflex during dynamic exercise would augment influences tending to cause a rise in arginine vasopressin, plasma renin activity, and catecholamines during dynamic exercise in humans. Ten healthy adults performed 30 min of supine cycle ergometer exercise at approximately 50% of peak oxygen consumption with or without moderate muscle metaboreflex activation by application of 35 mmHg lower body positive pressure (LBPP). Application of LBPP during the first 15 or last 15 min of exercise increased mean arterial blood pressure, plasma lactate concentration, and minute ventilation, indicating an activation of the muscle metaboreflex. These changes were rapidly reversed when LBPP was removed. During exercise at this intensity, LBPP augmented the release of arginine vasopressin and catecholamines but not of plasma renin activity. These results suggest that, although in humans hormonal responses are induced by moderate activation of the muscle metaboreflex during dynamic exercise, the thresholds for these responses may not be uniform among the various glands and hormones.