Effect of changes in posture on circulatory homeostasis in patients with the nephrotic syndrome

Summary. To assess whether the upright posture causes circulatory hypovolaemia in patients with the nephrotic syndrome (NS), we studied 12 subjects with NS and 12 healthy subjects during recumbency, 110 min of standing, followed again by recumbency. Control blood-pressure was 134/88±4/3 mmHg in the patients and 113/75±2/3 mmHg in the normal subjects (P<0.01), and remained higher in the patients throughout the procedure. Heart rate was continuously higher in the patients (P<0.05), but acceleration on standing was normal. The blood volume, which was not different during recumbency, had fallen below that in normal subjects after 25 min of standing (P<0.05), due to excessive plasma volume reduction (-16.8±0–8% in the patients against -11.7±1.2% in the normals, P<0.02). Plasma renin activity (PRA) was higher in the patients while recumbent (P<0.001) but not during standing, due to a blunted response in some. No significant differences in plasma noradrenaline were found, but four patients reacted with an excessive rise in plasma noradrenaline and heart rate. This subset, which had high PRA levels as well, comprised the only subject who experienced orthostatic hypotension. It is concluded that during standing an excessive drop in plasma volume leads to a lowered blood volume in NS patients. This forms a paradox with the heart rate acceleration and noradrenaline levels, which were mostly normal, and with the blood-pressure, which remained slightly elevated. Even in a few patients with enhanced stimulation of heart rate and noradrenaline, blood-pressure was found to be high in the majority of cases. PRA was usually found to be increased but, in part, independent of posture.     

The influence of autonomic diabetic neuropathy and human atrial natriuretic peptide on adrenal gland function in postural changes]

To investigate the influence of postural changes on plasma renin activity (PRA), plasma levels of human atrial natriuretic peptide (hANP) and on aldosterone in diabetes mellitus and autonomic neuropathy, ten patients with diabetes mellitus and autonomic neuropathy and ten patients with diabetes mellitus but without autonomic neuropathy were studied. Ten healthy subjects served as controls. Patients and controls were in supine position for 60 minutes, then changed posture sequentially to sitting (90 minutes) and to upright position (15 minutes). In controls, PRA was increased upon sitting and in the upright position, while hANP was decreased. Patients with autonomic neuropathy differed from controls in impaired renin stimulation, whereas in patients without autonomic neuropathy PRA responses to postural changes were only slightly decreased. In both groups of patients, the normal hANP responsiveness to postural changes was lacking. There were no differences in aldosterone levels between patients and controls. In patients with high basal hANP levels due to elevated systolic blood pressure renin responses to postural changes were decreased in comparison to those patients with low basal hANP levels. Thus, in patients with diabetes mellitus increased hANP levels which are not decreased in response to upright standing may contribute to the development of hyporeninism and its sequelae.     

Effect of bromocriptine treatment on prolactin, noradrenaline and blood pressure in hypertensive haemodialysis patients

Bromocriptine (2.5 mg/day orally) produced a significant fall in supine mean arterial pressure in nine hypertensive haemodialysis patients with high serum prolactin levels, without causing significant changes in heart rate. On bromocriptine, there was a significant decrease in the mean value of both serum prolactin and plasma noradrenaline, without significant changes in the mean value of plasma renin activity. A significant relationship was found between the changes in supine plasma noradrenaline and the changes in supine mean arterial pressure induced by bromocriptine. The increase in mean arterial pressure in response to the tilt test was greater on bromocriptine than on placebo although the changes in plasma noradrenaline were reduced by bromocriptine. Similar results were observed during the cold pressor test. These findings suggest that the arterial pressure-lowering effect of bromocriptine is related to the reduction in sympathetic out-flow. The parallel decrease in serum prolactin raises the question of the possible involvement of dopaminergic mechanisms in the development of hypertension in our patients. Moreover, bromocriptine seems to enhance the vascular response to endogenous noradrenaline.     

Plasma catecholamine responses to change of posture in alcoholics during withdrawal and after continued abstinence from alcohol

Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2-7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2-7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.     

Renal and cardiovascular effects of caffeine: a dose-response study

The effects of increasing oral doses of caffeine (45, 90, 180 and 360 mg) on effective renal plasma flow (ERPF), plasma renin activity (PRA), serum electrolytes, plasma noradrenaline, blood pressure and heart rate were studied in eight healthy male volunteers. Urine volume was increased by 360 mg of caffeine only. At caffeine doses greater than 90 mg urinary sodium excretion was significantly increased. There were no changes in ERPF. Serum potassium was significantly reduced by 360 mg of caffeine. Caffeine increased systolic pressure in a dose related manner. Diastolic pressure was also increased, but not in relation to dose. A 360 mg dose of caffeine produced a late increase in heart rate. These changes were not associated with any alterations in PRA or in plasma noradrenaline.     

慢性肾功能衰竭患者血液透析前后血管活性因子的变化及临床意义

目的了解血液透析患者血浆一氧化氮（NO）、内皮素（ET）、心房利钠多肽（ANP）、肾素（PRA）及血管紧张素Ⅱ（ATⅡ）在透析前后的水平变化及临床意义。方法设正常对照、慢性肾功能不全失代偿期患者及慢性肾功能衰竭（CRF）患者各30例。用比色法测定NO,放射免疫法测定ANP、ET、PRA及ATⅡ水平。结果CRF组NO、ANP、ET、PRA、ATⅡ浓度明显高于对照组（P<0.05或P<0.01）;透析后NO和ANP显著下降（P<0.05和P<0.01）,PRA和ATⅡ浓度明显升高（P均<0.01）,ET透析前后无明显变化（P>0.05）。结论血液透析可使CRF患者血浆NO、ANP降低,PRA、ATⅡ升高,提示ET升高可增加ANP和PRA水平,ANP浓度可抑制ATⅡ的分泌。     

Do elderly patients with an excessive fall in blood pressure on standing have evidence of autonomic failure?

1. Blood pressure, heart rate and plasma catecholamine responses were examined in two groups of elderly subjects distinguished by blood pressure responses to standing. Subjects in the control group showed a fall of less than 15 mmHg in systolic blood pressure on standing; subjects in the orthostatic hypotension group had falls of more than 20 mmHg systolic and 10 mmHg diastolic blood pressure on standing. 2. The heart pressure response on standing showed no significant difference between the two groups. 3. The orthostatic hypotension patients had lower plasma noradrenaline concentrations than the control patients (P less than 0.01) in the supine position, but during 10 min standing there was no significant difference in noradrenaline levels between the groups, and the percentage increase of noradrenaline levels in the orthostatic hypotension group was greater (P less than 0.05) than in the control group. 4. In the supine position, diastolic blood pressure was higher (P less than 0.05) in the orthostatic hypotension group than in the control group. 5. We conclude that impairment of baroreceptor function is not involved in most cases of orthostatic hypotension in the elderly, nor is there reduction of sympathetic nervous activity. We suggest that mechanical changes or adrenoreceptor dysfunction are more likely to be important factors in orthostatic hypotension in the elderly.     

Effect of acute vascular fluid volume expansion on erythrocyte sodium transport in essential hypertension

Evidence exists that volume expansion is associated with the appearance of a circulating sodium transport inhibitor. We have evaluated intra-arterial blood pressure (BP), central venous pressure (CVP), plasma renin activity (PRA), intraerythrocyte sodium content, erythrocyte sodium influx and rate constant of sodium efflux in 10 untreated primary hypertensive men (WHO stages I and II). The investigations were done during baseline conditions and after rapid intravenous infusion of 1 litre of saline (0.9% NaCl solution) over 15-20 min. Volume expansion caused an increase in CVP by 6.0 +/- 0.5 cmH2O (p less than 0.01), while BP only exhibited a slight increase. No significant changes in intraerythrocyte sodium content, sodium influx, sodium efflux rate constant or PRA were found after volume expansion compared to baseline. All patients with low normal PRA experienced a decrease in sodium efflux rate constant after volume expansion. We found a positive correlation between baseline PRA and change in sodium efflux rate constant after volume expansion (r = 0.62, p less than 0.05). At baseline the relationship between PRA and intraerythrocyte sodium content nearly reached statistical significance (r = 0.63, p = 0.054). These results may indicate that acute volume expansion influences the release of a circulating factor, modulating sodium transport in low-renin hypertension.     

Plasma levels and effects of metoprolol on blood pressure, adrenergic beta receptor blockade, and plasma renin activity in essential hypertension.

The effects of metoprolol, a selective beta adrenergic receptor antagonist, on blood pressure, beta receptor blockade (antagoinst of isoproterenol and exercise tachycardia), and plasma renin activity (PRA) have been compared with those of placebo in 16 patients with essential hypertension. The dose of metroprolol was 25 mg three times daily for 1 wk and thereafter 100 mg three times daily for 5 wk. The mean decrease in blood pressure during treatment with metoprolol was 24 +/- 3.8 (SEM)/10 +/- 2.1 mm Hg in the lying position and 23 +/- 4.4/9 +/- 3.1 mm Hg after 1 min in the standing position. At a dose of 2.9 to 5.4 mg/kg, steady-state plasma concentrations of metoprolol varied 17-fold (from 20 to 341 ng/ml) between patients and correlated with the interindividual variability in isoproterenol antagonism (r = 0.58, p less than 0.05) and decrease in exercise tachycardia (r = 0.65, p less than 0.01). By contrast, neither of these variables correlated with the dose of metoprolol in mg/kg. Metoprolol decreased PRA by 67 +/- 1.9 and 71 +/- 1.2% in the lying and standing positions, respectively. The decrease in the mean arterial blood pressure in the lying position was significantly correlated to the PRA during the placebo period (r = 0.61, p less than 0.05) but not to the plasma steady-state levels of metoprolol, the degree of beta receptor blockade, and the decrease in PRA.     

Cigarette smoke-induced elevation of plasma neuropeptide Y levels in man

Summary. The purpose of the present study was to evaluate whether neuropeptide Y, which coexists with noradrenaline in sympathetic nerves, may be released upon cigarette smoking. Therefore, previously non-smoking adults inhaled smoke from one cigarette once every minute during 10 min, and the effects on blood pressure, heart rate and plasma levels of noradrenaline and neuropeptide Y were analysed. A prompt rise of systolic blood pressure and heart rate (by 25 mmHg and 30 beats min^-1, respectively) was observed upon smoking. Systemic plasma levels of noradrenaline and neuropeptide Y were significantly elevated after 3 and 5 min of smoking, respectively, and reached maximal values (neuropeptide Y from 32±4 to 49± 7pmoll^-1, and noradrenaline from 0.72±0.16 to 1.8±0.44 nmol 1^-1) 2–5 min after the smoking period. It is concluded that smoking in man is associated with increased plasma levels of both noradrenaline and neuropeptide Y, suggesting release of these agents. Since neuropeptide Y is a potent vasoconstrictor, the present data suggest that this peptide may contribute to the smoke-induced cardiovascular response.     

The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients

Abstract. The studies were designed to explore the effect of the converting enzyme inhibitor captopril on the activity of the sympathetic nervous system during basal conditions and following graded physical exercise in patients with essential hypertension. Seven males and two females, aged 36–59 years, were hospitalized under metabolic ward conditions and treated for 7 days with captopril given orally in increasing dosages, the final dose being 600 mg daily. The patients were subjected to an individual, graded submaximal work test (bicycling) for 20 min before medication and then again in an identical manner during medication with 600 mg captopril. Blood samples were drawn before exercise and then after 10 and 20 min of work for the determination of plasma angiotensin II (PA II), plasma aldosterone (PAC), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma adrenaline (PA). Before medication blood pressure (mmHg) was 195/133 immediately before exercise, 230/129 after 10 min of moderate exercise and 263/105 following 20 min of nearly maximal work. During treatment with captopril the respective blood pressure values were 154/110, 200/100 and 245/98. Captopril had no significant effect on the changes in heart rate following physical exercise. PA II and PAC were substantially reduced and PRA considerably increased by captopril. PA II, PAC and PRA increased in response to exercise both before and following captopril. The exercise stimulated increase in PNA and PA was almost identical before and during captopril. Thus, captopril had no major effect on the activity of the sympathetic nervous system in patients with essential hypertension, neither during basic conditions nor during heavy physical exercise in spite of a profound decrease in PA II.     

Lack of effect of naloxone in a moderate dosage on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity and plasma aldosterone in healthy males

There is evidence that opioid peptides influence blood pressure and heart rate in animals and man. In the present investigation the effect of naloxone on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity (PRA) and plasma aldosterone was investigated in nine healthy men. A submaximal work test was performed on two occasions. The test consisted of ergometer bicycling for 10 min on 50% of maximal working capacity immediately followed by 10 min on 80% of maximal working capacity. Ten minutes before exercise the subjects received in a randomized manner a bolus dose of naloxone (10 micrograms/kg) or a corresponding volume of saline followed by a slow infusion (15 ml/h) of naloxone (5 micrograms h-1 kg-1) or saline, respectively. After exercise systolic blood pressure, heart rate, plasma catecholamines, PRA and plasma aldosterone increased during both saline and naloxone infusion. The changes were similar in both studies. Accordingly, opiate receptors sensitive to naloxone in a moderate dosage seem not to be involved in the cardiovascular response and the increase in plasma catecholamines, PRA and plasma aldosterone induced by exercise.     

Cardiac output and blood pressure during active and passive standing

Summary. The present study compared the haemodynamic pattern of active and passive standing. We used non-invasive techniques with beat-to-beat evaluation of blood pressure, heart rate and stroke volume. Seven healthy subjects, aged 24–41 (mean 30) years were examined. Finger blood pressure was continuously recorded by volume clamp technique (Finapres ®), and simultaneous beat-to-beat beat stroke volume was obtained, using an ultrasound Doppler technique, from the product of the valvular area and the aortic flow velocity time integral in the ascending aorta from the suprasternal notch. Measurements were performed at rest, during active standing and following passive tilt (60°). Active standing caused a transient but greater reduction of blood pressure and a higher increase of heart rate than passive tilt during the first 30 s (δ mean blood pressure: -39 ± 10 vs. -16 ± 7 mmHg, δ heart rate: 35 ± 8 vs. 12 ± 7 beats m^-1 (active standing vs. passive tilt; P < 0.01). There was a significantly larger increase in cardiac output during active standing (37 ± 24 vs. 0 ± 15%, P < 0.01) and a more marked decrease in total peripheral resistance (-58 ± 11 vs. -16 ± 17%, P < 0.01). A precipitous rise in intra-abdominal pressure (43 ± 22 mmHg) could be observed upon rising only in active standing. This was interpreted as an indication of translocation of blood to the thorax. There was no significant difference in haemodynamic changes during the later stage of standing (1–7 min) between both manoeuvres. These results suggest that active standing causes a marked blood pressure reduction in the initial phase which seems to reflect systemic vasodilatation caused by activation of cardiopulmonary baroreflexes, probably due to a rapid shift of blood from the splanchnic vessels in addition to the shift from muscular vessels associated with abdominal and calf muscle contraction. Moreover, the ultrasound Doppler technique was found to be a more adequate method for rapid beat-to-beat evaluation of cardiac output during orthostatic manoeuvres.     

Vasoactive neuroendocrine responses associated with tolerance to lower body negative pressure in humans

The purpose of this investigation was to test the hypothesis that peripheral vasoconstriction and orthostatic tolerance are associated with increased circulating plasma concentrations of noradrenaline, vasopressin and renin–angiotensin. Sixteen men were categorized as having high (HT, n=9) or low (LT, n=7) tolerance to lower body negative pressure (LBNP) based on whether the endpoint of their pre‐syncopal‐limited LBNP (peak LBNP) exposure exceeded ?60 mmHg. The two groups were matched for age, height, weight, leg volume, blood volume and maximal oxygen uptake, as well as baseline blood volume and plasma concentrations of vasoactive hormones. Peak LBNP induced similar reductions in mean arterial pressure in both groups. The reduction in legarterial pulse volume (measured by impedance rheography), an index of peripheral vascular constriction, from baseline to peak LBNP was greater (P<0·05) in the HT group (?0·041 ± 0·005 ml 100 ml^?1) compared to the reduction in the LT group (?0·025 ± 0·003 ml 100 ml^?1). Greater peak LBNP in the HT group was associated with higher (P<0·05) average elevations in plasma concentrations of vasopressin (pVP, Δ=+7·2 ± 2·0 pg ml^?1) and plasma renin–angiotensin (PRA, Δ=+2·9 ± 1·3 ng Ang II ml^?1 h^?1) compared to average elevations of pVP (+2·2 ± 1·0 pg ml^?1) and PRA (+0·1 ± 0·1 ng Ang II ml^?1 h^?1) in the LT group. Plasma noradrenaline concentrations were increased (P<0·05) from baseline to peak LBNP in both HT and LT groups, with no statistically distinguishable difference between groups. These data suggest that the renin–angiotensin and vasopressin systems may contribute to sustaining arterial pressure and orthostatic tolerance by their vasoconstrictive actions.     

Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension

The effect of spironolactone (50 mg b.i.d.) in essential hypertension was studied by measurement of effective renal plasma flow (ERPF), blood urea nitrogen (Ur+), serum creatinine (Cr), cardiac index (CI), plasma volume (PV), body weight (BW), mean arterial blood pressure (MAP), total peripheral resistance index (TPRI), plasma renin activity (PRA) and plasma aldosterone (PA) in two groups of patients. Ten cases had determinations before, after 5 weeks and 4 months of treatment; fourteen cases who had been treated at an average of 18 months, had measurements while on treatment and 5 weeks after cessation of the drug. Among the ten patients ERPF fell in six and increased in four patients during treatment, but was statistically unchanged in the total group. Ur + and Cr were also unchanged by treatment. ERPF was unchanged after withdrawal of the drug. During treatment BW decreased 3.5%, PV decreased in nine and increased in one patient, while PRA and PA increased 426% and 202%, respectively. After cessation of the aldosterone blockade, BW increased 1.9%, PV 10.5% while PRA and PA fell 60% and 48.9%, respectively. MAP fell in eight out of ten patients during treatment. This fall was associated with a fall in CI or TPRI, or both. After withdrawal of the drug, MAP increased in nine and decreased in five of the patients. The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA.     

Role of renin-angiotensin-aldosterone system in pathogenesis of arterial hypertension in chronic renal failure]

AIM: To characterize status of renin-angiotensin-aldosterone system (RAAS) in patients with chronic and terminal renal failure (CRF, TRF) and its role in pathogenesis of arterial hypertension (AH). MATERIALS AND METHODS: RAAS was studied in 90 patients with TRF on chronic hemodialysis (CHD) and 17 CRF patients with AH on conservative therapy. Plasma renin activity (PRA) and the level of plasma aldosterone (PA) were measured with radioimmunoassay. RESULTS: PRA with moderate CHD-controlled hypertension (1.16 ng/ml/h) was not higher than in control group (1.33 ng/ml/h), while in severe hypertension PRA was increased 4.6-fold (6.09, p < 0.05). In CRF with severe AH PRA was higher 3.6 times (4.8 ng/ml/h, p < 0.05). PA was in CRF and TRF patients 4-5 times higher than in healthy controls. A positive correlation was found between PRA and mean dynamic AP (r = 0.448, p < 0.01) and PRA with PA (r = 0.31, p < 0.05). CONCLUSION: A leading role of RAAS is shown in pathogenesis of AH in patients with hemodialysis uncontrolled hypertension and, partially, in patients with CRF and severe AH.     

New monitors of intravascular volume: a comparison of arterial pressure waveform analysis and the intrathoracic blood volume

Objective: Two new monitoring techniques, the analysis of arterial pressure waveform during mechanical ventilation and the determination of intrathoracic blood volume, were evaluated for preload assessment in a model of graded hemorrhage. Design: 8 anesthetized dogs bled of 10, 20, and 30 % of their blood volume, then retransfused and volume loaded with plasma expander. Central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), cardiac output, parameters of the arterial pressure waveform analysis [systolic pressure variation (SPV) and delta down (dDOWN)], and intrathoracic blood volume (ITBV) were measured at baseline and after each stage of hemorrhage and volume expansion. Results: The stroke volume index decreased significantly from 1.3 ± 0.4 ml/kg at baseline to 0.7 ± 0.2 ml/kg at 30 % hemorrhage and then increased after retransfusion and volume loading. The changes in the filling pressures during the various stages of hemorrhage were in the range of 1–2 mmHg. CVP decreased from 5.5 ± 0.9 to 3.1 ± 1.7 mmHg and PCWP from 8.0 ± 0.8 to 5.1 ± 1.2 mmHg at 30 % hemorrhage. Both filling pressures responded significantly to retransfusion; PCWP also changed in response to a volume load. SPV and dDOWN (expressed as percent of the systolic blood pressure during a short apnea) increased significantly from 6.7 ± 1.7 and 5.6 ± 3.2 %, respectively, at baseline, to 9.7 ± 2.6 and 8.1 ± 2.9 % after 10 % blood loss and to 13.1 ± 3.9 and 11.1 ± 3.8 % after 30 % hemorrhage. ITBV decreased significantly from 29.7 ± 4.5 to 26.8 ± 5.3 ml/kg after 10 % blood loss and to 23.1 ± 3.0 ml/kg after 30 % hemorrhage. ITBV, SPV, and dDOWN responded significantly to retransfusion and volume load. Significant correlations were found between the degree of volume change and dDOWN (r = 0.93), SPV (r = 0.96), ITBV (r = 0.95), CVP (r = 0.82), and PCWP (r = 0.90). Conclusions: The parameters of arterial pressure waveform analysis (SPV and dDOWN) and ITBV were sensitive estimates of cardiac preload during the early stages of hemorrhage. Measurement of SPV and dDOWN, being both sensitive and relatively noninvasive, has advantages over other methods of preload assessment but is limited to patients on controlled mechanical ventilation. ITBV, which supplies quantitative information about cardiac preload, is more invasive but can also be used in patients who are breathing spontaneously or who are on partial ventilatory support. Received: 6 June 1996 Accepted: 27 February 1977     

Plasma renin and serum dopamine-beta-hydroxylase during orthostatic hypotension in quadriplegic man

To determine whether orthostatic hypotension in patients with cervical spinal cord lesions is the result of impaired sympathetic nerve response and/or impaired renin release, serum dopamine-beta-hydroxylase (DbetaH) activity and plasma renin activity (PRA) were examined during passive tilting in 6 quadriplegic patients and in 6 able-bodied control subjects. Serum DbetaH was measured by an isotopic enzymatic method and PRA by radioimmunoassay. Following head-up tilting, quadriplegic subjects demonstrated a prompt, significant decrease in mean arterial pressure (MAP) and increase in heart rate (HR). DbetaH and PRA both increased significantly 15 minutes after tilt. In normal subjects, although HR increased, MAP was unchanged; DbetaH and PRA did not increase significantly during head-up tilt. The finding of increased DbetaH during tilt hypotension in quadriplegic patients provides evidence that reflex sympathetic nerve stimulation persists despite cervical cord transection. Increased PRA may be attributed to decreased renal perfusion pressure and increased sympathetic stimulation during tilt hypotension. These data suggest that orthostatic hypotension in quadriplegia patients cannot be attributed solely to failure of the sympathetic nervous system or the renin-angiotensin system to respond to the stimulus of orthostasis.     

Dose response in captopril therapy of hypertension

Dose-response curves of blood pressure and of the biochemical components of the renin-angiotensin-aldosterone system were determined during long-term treatment with captopril in 21 hypertensive patients. Captopril was given in biweekly, doubling doses starting with 25 mg 3 times a day until control of blood pressure was achieved or a total daily dosage of 600 mg was reached. Recumbent and standing systolic and diastolic blood pressure fell on 75 mg captopril daily. Increasing the captopril dose did not induce further significant hypotensive effects. The pretreatment level of plasma renin activity (PRA) was a poor predictor of the hypotensive effect of captopril. The rises in PRA and plasma angiotensin I level (PA I) and the decrease in plasma angiotensin II level (PA II) and plasma aldosterone level (PAC) provide biochemical evidence for angiotensin-converting enzyme (ACE) inhibition in vivo. These effects were present on daily doses of 75 to 150 mg captopril.     

Effects of 1-sarcosine-8-isoleucine-angiotensin II on blood pressure and plasma renin activity in various types of hypertension.

The pharmacological effects of 1-Sar-8-Ile-angiotensin II on blood pressure and plasma renin activity (PRA) were studied in 5 normal subjects and in 19 patients with hypertension of various etiologics including malignant hypertension, renovascular hypertension, essential hypertension, and primary aldosteronism. Intravenous administration of this peptide induced a significant pressor response in normal or low PRA subjects at infusion rates of 100-600 ng/kg/min. Similar pressor response was also observed in renovascular hypertensives with normal PRA who were cured later by surgical treatment. The blood pressure in high PRA group was lowered remarkably by infusion of this angiotensin II inhibitor. A significant increase in PRA was obtained in subjects with malignant hypertension following the infusion of this peptide. However, there was no detectable rise in PRA in other subjects with normal or high PRA. The present data show that circulating angiotensin II plays an important role in maintaining high blood pressure in high PRA patients, especially in malignant hypertension, while it is not directly involved in the maintenance of high blood pressure in human chronic renovascular hypertension.