Heterologous radioimmunoassay of atrial natriuretic polypeptide in dog and rabbit plasma

Atrial natriuretic peptide (ANP) was measured in plasma of dogs and rabbits by radioimmunoassay (RIA) using a commercially available anti alpha-ANP serum and compared to our measurements of ANP in rats and humans. Plasma concentration of ANP in dog coronary sinus (234.9 +/- 41.0 pg/ml) was significantly greater than in systemic arterial blood (81.2 +/- 8.4 pg/ml). Gel filtration of dog coronary sinus plasma resulted in an ANP peak with the elution volume (Ve) of synthetic atriopeptin III (AIII) and a minor peak eluting with the void volume (Vo). Rabbit systemic arterial plasma ANP was 53.3 +/- 4.3 pg/ml and yielded one peak, with a Ve of AIII. Ion exchange chromatography of dog and rabbit atrial extracts (AE) resulted in a major ANP region which resembled AIII. Gel filtration of AE showed larger molecular species as well as AIII. Dilutions of dog and rabbit plasma and AE were parallel with the AIII standard in radioimmunoassay.     

Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

Effects of receptor blockade on metabolism and renal actions of vasopressin in conscious dogs

Vasopressin – but not the V₂ receptor agonist [deamino-cis1,D-Arg8]-vasopressin (dDAVP) – may mediate natriuresis in dogs. The present study investigated this phenomenon by use of nonpeptide antagonists to V_1a and V₂ receptors 1-{1-[4- (3-acetylaminopropoxy)benzoyl]-4-piperidyl}-3,4-dihydro-2 (1H)-quinolinone (OPC-21268) and 5-dimethylamino-1-{4- (2-methylbenzoylamino)-benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260), respectively) hypothesising that only V_1a inhibition would reduce the natriuresis. In conscious dogs vasopressin secretion was suppressed by water loading (2% body weight) and replaced by infusion of vasopressin (50 pg min^?1 kg^?1) resulting in physiological plasma concentrations (plasma levels of AVP (pAVP) = 2.0 ± 0.1 pg mL^?1). In this setting, OPC-21268 did not change the rate of sodium excretion. OPC-31260 increased water excretion 12-fold without significant changes in sodium excretion. Heart rate, mean arterial blood pressure, glomerular filtration rate, and clearance of endogenous Li⁺ were unchanged. During vasopressin infusion, both antagonists increased pAVP, OPC-21268 by 20% and OPC-31260 by 100% (2.0 ± 0.2–4.0 ± 0.3 pg mL^?1). In the absence of vasopressin infusion, OPC-31260 did not increase pAVP. Thus, the increase in pAVP appeared to be due to a decrease in metabolic clearance rate. The results indicate that the present dose of V_1a receptor inhibitor OPC-21268 does not reduce sodium excretion and that both vasopressin antagonists inhibit vasopressin metabolism.     

ANP gene expression in rat hearts during hypoxia

 It is unclear whether the increase in plasma atrial natriuretic peptide (ANP) concentration during hypoxia is due to direct, hypoxia-induced upregulation of ANP secretion in the heart, or to pressure overload of the right ventricle (RV) following hypoxia-induced pulmonary hypertension. To test the hypothesis that hypoxia leads to an early upregulation of the ANP gene, we examined the influence of acute and prolonged inspiratory hypoxia (6 h, 1 or 3 weeks) on the expression of ANP messenger ribonucleic acid (mRNA) in rat heart and compared the results with the expression of the ANP gene after acute pressure overload induced by experimental coarctation of the main pulmonary artery. As a molecular marker for hypertrophy we determined the ratio of α- and β-myosin gene expression. Hypoxia increased systolic RV pressure from 20.0 ± 1.6 mmHg to 27.8 ± 1.6 mmHg (P < 0.01) and 41.6 ± 2.1 mmHg (P < 0.05) after 1 and 3 weeks hypoxia respectively. The ANP plasma concentration did not change significantly after 6 h or 1 week: 232 ± 21 pg/ml (control), 246 ± 25 pg/ml (6 h), 268 ± 25 pg/ml (1 week), but increased significantly after 3 weeks hypoxia (446.8 ± 99.56 pg/ml; P < 0.05). ANP mRNA levels in different regions of the heart did not change after 6 h or 1 week hypoxia. After 3 weeks hypoxia ANP mRNA had increased 2.7-fold in the RV (P < 0.05), 4.2-fold in the left ventricle (LV, P < 0.05), 3.5-fold in the septum (S, P < 0.05) and about 1.4-fold in the right (n.s.) and left atrium (n.s.). Relative ventricular masses increased significantly only for the RV (190%, P < 0.05) during hypoxia. The β/α-myosin mRNA ratio did not change after 6 h hypoxia but, contrary to ANP gene expression, increased after just 1 week (6.1-fold in RV, 7.8-fold in LV, 6-fold in S; P < 0.05) and was more pronounced in the RV after 3 weeks (9.4-fold in RV, 7.6-fold in LV, 9.1-fold in S; P < 0.05). The increase in the β/α-myosin mRNA ratio in the LV contrasts with a lack of increase in relative ventricular mass. Acute pressure overload in the RV after pulmonary arterial banding significantly increased ANP-mRNA and the β/α-myosin mRNA ratio after 1 day in the RV. In the LV ANP mRNA was unchanged. The delayed upregulation of the ANP gene suggests that hypoxia per se is not a significant stimulus for ANP gene expression in the heart and that hypoxia-induced ANP-gene expression in the heart is regulated predominantly by the increase in RV afterload due to hypoxia-induced increased pulmonary pressure. The upregulation of ANP and β-myosin mRNA in the LV during chronic hypoxia has yet to be elucidated. Received: 5 November 1996 / Received after revision and accepted: 24 January 1997     

The existence of low concentrations of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid which does not correlate with plasma ANP levels

Atrial natriuretic peptide (ANP) concentrations in the cerebrospinal fluid (CSF) and plasma of canine were 2.1 +/- 1.1 pg/ml (mean +/- S.D.) and 53.1 +/- 21.1 (n = 20), respectively. The regression coefficient between these concentrations was -0.0045 (P = n.s.). The ANP concentration in the CSF did not change even after the plasma ANP concentration was altered following the change of left atrial pressure, as in 4 cases of an experimental aortic regurgitation. Thus, ANP concentration in the CSF is not influenced by ANP concentrations in the plasma at least under our condition. Gel permeation chromatography revealed a single form of ANP in the position of authentic alpha-ANP in canine CSF, while a high molecular weight ANP peak was observed as well as alpha-ANP in the plasma.     

Pituitary–adrenal responses to arm versus leg exercise in untrained man

The purpose of this study was to examine pituitary–adrenal (PA) hormone responses [beta-endorphin (β-END), adrenocorticotropic hormone (ACTH) and cortisol] to arm exercise (AE) and leg exercise (LE) at 60 and 80% of the muscle-group specific VO₂ peak. Eight healthy untrained men (AE VO₂ peak=32.4±3.0 ml kg⁻¹ min⁻¹, LE VO₂ peak=46.9±5.3 ml kg⁻¹ min⁻¹) performed two sub-maximal AE and LE tests in random order. Plasma β-END, ACTH and cortisol were not different (P>0.05) between AE and LE at either exercise intensity; the 60% testing elicited no changes from pre-exercise (PRE) values. For 80% testing, plasma β-END, ACTH and cortisol were consistently, but not significantly, greater during LE than AE. In general, plasma β-END and ACTH were higher (P<0.05) during 80% exercise, than PRE, for both AE and LE. Plasma cortisol was elevated (P<0.05) above PRE during 80% LE, and following 80% for both AE and LE. Plasma ACTH was higher (P<0.05) during 80% LE and AE versus 60% LE and AE, respectively. Plasma β-END and cortisol were significantly higher during and immediately after 80% LE than 60% LE. Thus, plasma β-END, ACTH and cortisol responses were similar for AE and LE at the two relative exercise intensities, with the intensity threshold occurring somewhere between 60 and 80% of VO₂ peak. It appears that the smaller muscle mass associated with AE was sufficient to stimulate these PA axis hormones in a manner similar to LE, despite the higher metabolic stress (i.e., plasma La^-) associated with LE.     

Solid Phase Radioimmunoassay for Direct Measurement of Human Plasma Oxytocin

Synthetic oxytocin (OT) conjugated to bovine thyroglobulin by the carbodiimide reaction was injected into rabbits to raise a high titre, specific OT antiserum which was then coupled to microcrystalline cellulose activated by cyanogen bromide. High affinity of the coupled antiserum was defined by Scatchard analysis, Keq = 7.1 ± 10¹¹l/mol. Cross-reactivity studies revealed little binding of antiserum to analogues of OT. lodination was performed by the Chloramine T method, giving specific activity of ¹²⁵I-OT, range 1.1–1.7 ± 10³ Cl/mmol. After incubation for 40 hours under disequilibrium conditions, specific and non-specific bindings were 10.6 ± 2.7% and 0.2 ± 0.1% (n=15), respectively. Displacement of 50% ¹²⁵I-OT occurred with 2.9 pg OT/tube. Coefficients of variation of standard OT concentrations (0.03–16 pg/tube) were < 5%. Limit of detection was 2 pg OT/ml plasma. Recovery of synthetic OT added to non-pregnant plasma was 81.8% (n=34) at 20 pg/ml and 97.4% (n=32) at 100 pg/ml. Two patients, 17 and 18 weeks post-partum, had increases in plasma OT from < 2 pg/ml to 18.3 and 16.0 pg/ml after 6 and 4 minutes breast feeding infants, respectively. We conclude that this solid phase OT radioimmunoassay is quick, relatively sensitive and reliable, and does not require prior extraction of plasma samples.     

Effects of atrial natriuretic peptide on systemic and renal hemodynamics and renal excretory function in patients with chronic renal failure

Summary We examined the effects of 60 min-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m² and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6±9.1 vs 13.6±1.9 pmol/l,p<0.05; cGMP: 14.3±2.9 vs 6.6±1.1 pmol/ml,p<0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5±3.2 vs. 17.3±1.3 pmol/ml,p<0.05). During ANP infusion, GFR increased in CRF by 70.7±4.2% from 34.5±6.8 to 57.4±9.9 ml/min/1.73m² (p<0.001) as compared to 16.2±1.4% in C (p<0.001 vs CRF). RBF increased in CRF by 43.6±6.4% and in C by 3.1±1.2% (p<0.01). Basal urinary sodium excretion (U_NaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, U_NaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FE_Na), however, was more pronounced in C. Basal FE_Na was higher in CRF (12.8±2.5% vs 2.4±1.5% in C,p<0.001), FE_Na remained elevated at 180% over baseline in C sixty minutes after cessation of ANP infusion, while it had returned to baseline in CRF. During ANP infusion, CI increased in CRF after 30 min from 2.91±0.08 to 3.12±0.091/min/m² (p<0.001) and in C from 3.20±0.11 to 3.39±0.13 l/min/m² (p< 0.05). Mean arterial BP was higher in CRF and its decrease was greater than in C (21.1±2.7% vs 9.1±1.0%,p<0.001). In patients with CRF GFR, RPF, and CI remained significantly elevated and BP was still significantly decreased 60 min after ANP infusion. Total peripheral vascular resistance (TPR) was elevated in CRF and declined during ANP infusion in both CRF and C. The decline of TPR was sustained and more pronounced in CRF than in C. Renal vascular resistance (RVR) was high in CRF and dropped by nearly 50% during ANP infusion, whereas only a moderate decline in RVR during ANP application was observed in C. Thus, exogenous ANP had greater and prolonged effects on systemic hemodynamics and renal function in CRF than in C. They may be due to higher levels of ANP following ANP infusion and appear to be mediated by a more sustained formation of the second messenger cGMP.Abbreviations ANP atrial natriuretic peptide - CRF chronic renal failure; - GFR glomerular filtration rate - FF filtration fraction - ERPF effective renal plasma flow - ERBF effective renal blood flow - BP blood pressure - MAP mean arterial blood pressure - HR heart rate - SV stroke volume - CO cardiac output - CI cardiac index - TPR total peripheral resistance - RVR renal vascular resistance - U_NaV urinary sodium excretion - FE_Na fractional sodium excretion - PRA plasma renin activity - ECFV extracellular fluid volume - PAH paminohippuric acid Dedicated to Prof. Dr. med. F. Krück on the occasion of his 70th birthday     

The use of a monoclonal antibody for the determination of atrial natriuretic peptides in human plasma

Summary A monoclonal antibody (mab) directed against -human atrial natriuretic peptides (-hANP) was produced. Using this mab a radioimmunoassay for the determination of hANP-like immunoreactivity in human plasma was established. To demonstrate the possible application of this radioimmunoassay for clinical diagnosis, plasma levels were measured in healthy subjects and in patients with renal failure before and after hemofiltration or hemodialysis. Plasma levels in healthy subjects ranged between less than 30 and 124 pg/ml. Mean plasma concentrations of hANP-IR in uremic subjects were 324 pg/ml before and 113 pg/ml after hemofiltration or hemodialysis.Abbreviations ANP atrial natriuretic peptides - hANP human atrial natriuretic peptide - hANP-IR hANP-like immuno-reactivity - HPLC high performance liquid chromatography - mab monoclonal antibody - RIA radioimmunoassay     

Soluble interleukin-2 receptor and interleukin-8 plasma levels during and after cardiopulmonary bypass: correlations with creatine kinase and creatine kinase MB

In this study, soluble receptor of interleukin-2, interleukin-8, creatine kinase, and creatine kinase MB isoenzyme levels were determined serially before, during, and after cardiopulmonary bypass in blood samples of 24 patients. Interleukin-2 receptor levels were 683±80 U/ml in the preoperative period and 640±60 U/ml during hyperthermia. Subsequently, these levels increased significantly at the end of the procedure (791±70 U/ml, P<0.01), remaining elevated 1 h after (882±92 U/ml, P<0.001) and reaching peak values 24 h postoperatively (1,752±200 U/ml, P<0.001). Preoperative plasma values of interleukin-8 were 230±43 pg/ml. Interleukin-8 concentrations were 185±25 pg/ml during hypothermia. The peak interleukin-8 levels were observed at the end of cardiopulmonary bypasss (754±94 pg/ml, P<0.001) and tended to decrease 1 h after the procedure (643±76 pg/ml, P<0.001), declining to preoperative values, 24 h postoperatively (273±41 pg/ml). Interleukin-2 receptor levels correlated well with creatine kinase levels during the procedure. Furhtermore, creatine kinase MB levels were correlated with interleukin-2 receptor values only at the end and 1 h after completion of cardiopulmonary bypass. We concluded that interleukin-8 and Interleukin-2 receptor levels are elevated after cardiopulmonary bypass and may contribute to myocardial injury as reflected by increased levels of creatine kinase and creatine kinase MB and correlations between interleukin-2 receptor and both creatine kinase and creatine kinase MB levels. Received: 17 July 2000 / Accepted: 12 February 2001     

血清BNP浓度与肺静脉消融术后房颤复发关系的研究

目的:研究房颤患者经肺静脉消融后房颤复发与血清脑利钠肽(BNP)之间的关系。方法:采用化学免疫荧光检测法检测68例左室射血分数正常的房颤患者(阵发性房颤48例,持续性房颤20例)消融前血清BNP浓度,两组患者均于术后3个月接受72hHolter监测以观察房颤复发。结果:消融前阵发性房颤组血清BNP浓度低持续性房颤组(81.40±15.20pg/mlvs142.5±32.60pg/ml,P0.05),阵发性房颤消融术后复发房颤10例(20.9%),其血清BNP浓度较未复发者增高(144.30±20.41pg/mlvs68.5±25.30pg/ml,P0.05).持续性房颤消融术后9例(45.00%)复发房颤,其血清BNP浓度(193.35±30.25pg/ml)显著高于未复发者及阵发性房颤复发者。结论:房颤患者消融术前血清BNP浓度同肺静脉消融术后房颤复发有关;血清BNP浓度可能对提高房颤消融成功有积极意义。     

Pathophysiological adaptations to walking and cycling in primary pulmonary hypertension

Exercise tolerance inversely correlates with the severity of the disease in patients with idiopathic pulmonary arterial hypertension (IPAH). Cycling and walking protocols are commonly utilized in the evaluation of exercise intolerance in IPAH, but little information exists on possible differences in ventilatory and gas exchange adaptations to these exercise modalities. In a group of patients with moderate to severe IPAH (n = 13), we studied the ventilatory, cardiovascular and gas exchange adaptations to maximal incremental walking (W) and maximal incremental cycling (C). During W, compared to C, the ventilatory equivalents for CO₂ output (V′_E/V′CO₂) were significantly higher either expressed as the rate of increment (56 ± 5 vs. 45 ± 3; P < 0.0001) or as the absolute values at anaerobic threshold (AT) and at peak exercise. At AT, the increase in V′_E/V′CO₂ during W was associated with a significant lower value of end-tidal carbon dioxide. At peak W, compared to peak C, dyspnea sensation was higher and arterial oxygen saturation (SpO₂) was lower (87 ± 2 vs. 91 ± 2, P < 0.001). In patients with IPAH the physiologic information obtained with W are different from those obtained with C. Tolerance to W exercise is limited by high ventilatory response and dyspnea sensation. W should be used to assess the degree of lung gas exchange inefficiency and arterial O₂ desaturation during exercise.     

Calciuresis elicited by spontaneous rehydration in dehydrated sheep

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg^-1 min^-1) were investigated in conscious dogs. In addition, the disappearance of ET-l in arterial and central venous plasma after an infusion of 10 ng kg^-1 min^-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg^-1 min^-1) and angiotensin II (AII, 2, 5, and 10 ng kg^-1 min^-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 ± 0.3 to 243 ± 23 pg ml^-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 ± 4 to 29 ± 3 ml min^-1 and 87 ± 16 to 71 ± 14 μmol min^-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t_½ was 1.1 ± 0.1 min. Vasopressin increased arterial blood pressure (107 ± 4 to 136 ± 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin – in contrast to angiotensin II – is able to increase the plasma concentration of ET-1. The latter may suggest that ET-1 is involved in the prolonged pressor action of AVP observed.     

Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans

We sought to determine the influence of sildenafil on the diffusing capacity of the lungs for carbon monoxide (DL_CO) and the components of DL_CO (pulmonary capillary blood volume V _c, and alveolar–capillary membrane conductance D _M) at rest and following exercise with normoxia and hypoxia. This double-blind placebo-controlled, cross-over study included 14 healthy subjects (age = 33 ± 11 years, ht = 181 ± 8 cm, weight = 85 ± 14 kg, BMI = 26 ± 3 kg/m², peak normoxic VO₂ = 36 ± 6 ml/kg, mean ± SD). Subjects were randomized to placebo or 100 mg sildenafil 1 h prior to entering a hypoxic tent with an FiO₂ of 12.5% for 90 min. DLCO, V _c, and D _M were assessed at rest, every 3 min during exercise, at peak exercise, and 10 and 30 min post exercise. Sildenafil attenuated the elevation in PAP at rest and during recovery with exposure to hypoxia, but pulmonary arterial pressure immediately post exercise was not different between sildenafil and placebo. Systemic O₂ saturation and VO_2peak did not differ between the two conditions. DL_CO was not different between groups at any time point. V _C was higher with exercise in the placebo group, and the difference in D _M between sildenafil and placebo was significant only when corrected for changes in V _c (D _M/V _c = 0.57 ± 0.29 vs. 0.41 ± 0.16, P = 0.04). These results suggest no effect of sildenafil on DLCO, but an improvement in D _M when corrected for changes in V _c during short-term hypoxic exposure with exercise.     

Influence of ingested fluid volume on physiological responses during prolonged exercise

The effect of different rates of fluid ingestion on heart rate, rectal temperature, plasma electrolytes, hormones and performance was examined during prolonged strenuous exercise conducted at 21 °C. Seven well-trained males (24 ± 1 yr; 68.6 ± 2.9 kg; Vo ₂ peak = 4.69 ± 0.17 L min^?1; mean ± SEM) cycled for 2 h at 69 ± 1% Vo ₂ peak while receiving either no fluid replacement (NF), a volume of water estimated to prevent body weight loss (FR-100 = 2.32 ± 0.10 L 2 h^?1) or 50% of this volume (FR-50 = 1.16 ± 0.05 L 2 h^?1). The 2-h exercise bout was followed by a ride to exhaustion at a workload estimated to be 90% Vo ₂ peak. After 2 h of exercise, NF was associated with a 3.2 ± 0.1% weight loss, while FR-50 and FR-100 resulted in losses of 1.8 ± 0.1 and 0.1 ± 0.1%, respectively. Compared with FR-100, heart rate and rectal temperature were elevated (P < 0.05) during the second hour of exercise in NF, with FR-50 intermediate. Reductions in plasma volume during exercise were greater in NF and FR-50, compared with FR-100 and plasma sodium concentration was elevated in NF, decreased slightly in FR-100, with FR-50 intermediate. Plasma renin activity, aldosterone and atrial natriuretic peptide increased to similar extents in the three trials. Plasma vasopressin remained unchanged for FR-100, increased for NF, with intermediate values for FR-50. Exercise time to exhaustion at 90% Vo ₂ peak was longer in FR-100 (328 ± 93 s) than NF (171 ± 75 s) with FR-50 (248 ± 107 s) not significantly different from either FR-100 or NF. In conclusion, the responses of heart rate, rectal temperature, plasma sodium, and vasopressin during, and performance following, prolonged cycling exercise conducted at 21 °C are related to the amount of fluid ingested (i.e. the degree of dehydration).     

Non-invasive haemodynamic assessments using Innocor™ during standard graded exercise tests

Cardiac output (Q) and stroke volume (V _S) represent primary determinants of cardiovascular performance and should therefore be determined for performance diagnostics purposes. Since it is unknown, whether measurements of Q and V _S can be performed by means of Innocor™ during standard graded exercise tests (GXTs), and whether current GXT stages are sufficiently long for the measurements to take place, we determined Q and V _S at an early and late point in time on submaximal 2 min GXT stages. 16 male cyclists (age 25.4 ± 2.9 years, body mass 71.2 ± 5.0 kg) performed three GXTs and we determined Q and V _S after 46 and 103 s at 69, 77, and 85% peak power. We found that the rebreathings could easily be incorporated into the GXTs and that Q and V _S remained unchanged between the two points in time on the same GXT stage (69% peak power, Q: 18.1 ± 2.1 vs. 18.2 ± 2.3 l min⁻¹, V _S: 126 ± 18 vs. 123 ± 21 ml; 77% peak power, Q: 20.7 ± 2.6 vs. 21.0 ± 2.3 l min⁻¹, V _S: 132 ± 18 vs. 131 ± 18 ml; 85% peak power, Q: 21.6 ± 2.4 vs. 21.8 ± 2.7 l min⁻¹, V _S: 131 ± 17 vs. 131 ± 22 ml). We conclude that Innocor™ may be a useful device for assessing Q and V _S during GXTs, and that the adaptation of Q and V _S to exercise-to-exercise transitions at moderate to high submaximal power outputs is fast enough for 1 and 2 min GXT stage durations.     

Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system

Aims: The study was designed to determine (i) whether the effects of angiotensin III (AngIII) are similar to those of angiotensin II (AngII) at identical plasma concentrations and (ii) whether AngIII operates solely through AT₁‐ receptors. Methods: Angiotensin II (3 pmol kg^?1 min^?1–3.1 ng kg^?1 min^?1) or AngIII (15 pmol kg^?1 min^?1–14 ng kg^?1 min^?1) was infused i.v. during acute inhibition of angiotensin converting enzyme (enalaprilate; 2 mg kg^?1) and of aldosterone (canrenoate; 6 mg kg^?1 plus 1 mg kg^?1 h^?1). Arterial plasma concentrations of angiotensins were determined by radioimmunoassay using a cross‐reacting antibody to AngII. During ongoing peptide infusion, candesartan (2 mg kg^?1) was administered to block the AT₁‐receptors. Results: Angiotensin immunoactivity in plasma increased to 60 ± 10 pg mL^?1 during infusion of AngII or infusion of AngIII. AngII significantly increased mean arterial blood pressure (+14 ± 4 mmHg) and plasma aldosterone by 79% (+149 ± 17 pg mL^?1) and reduced plasma renin activity and sodium excretion (?41 ± 16 mIU L^?1 and ?46 ± 6 μmol min^?1 respectively). AngIII mimicked these effects and the magnitude of AngIII responses was statistically indistinguishable from those of AngII. All measured effects of both peptides were blocked by candesartan. Conclusion: At the present arterial plasma concentrations, AngIII is equipotent to AngII with regard to effects on blood pressure, aldosterone secretion and renal functions, and these AngIII effects are mediated through AT₁‐ receptors. The metabolic clearance rate of AngIII is five times that of AngII.     

Vasopressin in cerebrospinal fluid and plasma of man, dog, and rat

Arginine-8-vasopressin (AVP) levels were measured by a sensitive and specific radioimmunoassay (RIA) in plasma and cerebrospinal fluid (CSF) of three species man, dog, and rat (Wistar and the Brattleboro strain). Basal plasma values were 1.7 pg/ml in Wistar rat, and 2.4 pg/ml in dog. Pentobarbitone, used as anesthetic during collection of CSF from dog and rat, caused a significant rise of plasma AVP values in Wistar rats, but not in dogs. After withdrawal of CSF, the plasma AVP levels of Wistar rats were increased to 29.5 +/- 9.5 pg/ml, whereas the CSF levels from the same animals were 11.5 +/- 3.9 pg/ml. The response to the various stimuli was similar in Brattleboro rats, heterozygous for hereditary hypothalamic diabetes insipidus, and in Wistar rats. In Brattleboro rats, homozygous for hereditary hypothalamic diabetes insipidus, AVP was neither detectable in plasma nor in CSF. In dog and man, AVP levels in CSF samples were higher than in simultaneously obtained plasma samples. The possibility that AVP present in CSF, might be released directly from the synthetizing hypothalamic nuclei into the ventricular system is discussed.     

Atrial natriuretic peptide and its mRNA in heart and brain of vasopressin-deficient Brattleboro rats

To understand the secretion and synthesis of atrial natriuretic peptide we measured immunoreactive atrial natriuretic peptide from plasma, heart tissues and brain areas, and ANP mRNA was determined from heart auricles and ventricles of vasopressin-deficient Brattleboro rats (DI) and from desmopressin treated Brattleboro rats (DI + DDAVP). Long-Evans rats (LE) served as controls. DI + DDAVP rats were given for 3 days sc. injections of 0.5/g l-desamino-8-D-arginine vasopressin in 1 ml. saline twice a day. The rats were housed in single metabolic cages and urinary output and water intake were measured daily. All the body and organ weight parameters were similar in the three groups when the rats were killed. No change was seen in the plasma ANP level between the groups. The right ventricle of DI + DDAVP rats had significantly (P < 0.05) higher concentration of ANP than LE rats (15.8 + 4.4 vs. 3.4 + 0.6 ng mg“¹ tissue). The left ventricle of DI and DI+DDAVP had significantly (P < 0.05) lower amounts of ANP mRNA than LE rats (0.5 ± 0.2 vs. 1.3 + 0.2 and 0.5 + 0.1 vs. 1.3 + 0.2 arbitrary units). In the hypothalamus, the ANP concentration was significantly (P < 0.05) lower both in DI and in DI + DDAVP rats than in LE rats (9.3 ±1.3 vs. 14.5 ±±1.6 and 6.1+0.6 vs. 14.5 ± 1.6 pg mg^-1 tissue). To conclude, although the water intake and urinary output of DI rats were changed towards normal with desmopressin treatment, the heart ventricular and hypothalamic ANP did not parallel the change. Desmopressin increased the ANP concentration in the right ventricle of DI rats. Thus the correction of the complete vasopressin deficiency-does not appear to associate with synthesis or release of atrial natriuretic peptide in heart or hypothalamus.     

Effects of short-term endurance exercise training on vascular function in young males

We investigated effects of 6 days of endurance exercise training [cycling at 65% of peak oxygen consumption (VO_2peak) for 2 h a day on six consecutive days] on vascular function in young males. Measures of VO_2peak, arterial stiffness, calf vascular conductance and heart rate variability were obtained pre- and post-training. Indices of arterial stiffness were obtained by applanation tonometry to determine aortic augmentation index normalized to a heart rate of 75 bpm (AI _x @75 bpm), and central and peripheral pulse wave velocity (CPWV, PPWV). Resting and maximal calf vascular conductances were calculated from concurrent measures of blood pressure and calf blood flow using venous occlusion strain-gauge plethysmography. Time and frequency domain measures of heart rate variability were obtained from recording R–R intervals during supine and standing conditions. Both CPWV (5.9 ± 0.8 vs. 5.4 ± 0.8 m/s) and PPWV (9.7 ± 0.8 vs. 8.9 ± 1.3 m/s) were reduced following the training program. No significant changes were observed in AI _x @75 bpm, vascular conductance, heart rate variability or VO_2peak. These data indicate that changes in arterial stiffness independent of changes in heart rate variability or vascular conductance can be achieved in healthy young males following only 6 days of intense endurance exercise.