Cardiovascular and endocrine responses to haemorrhage in the pig

Heart rate (HR), mean arterial pressure (MAP), indices of sympathetic and parasympathetic activity (plasma concentrations of adrenaline, noradrenaline and pancreatic polypeptide, PP), vasopressin (VP) and aldosterone (ALDO) were measured in six pigs during continuous bleeding resulting in hypovolaemic shock, from which five survived. Three stages of haemorrhage could be defined. Stage I. Resting MAP was 85 ± 6 mmHg and increased to 96 ± 5 mmHg with a blood loss of 275 (range 250–300) (10 (9–12)% of the estimated blood volume) concomitant with an increase in HR from 105 ± 5 to 113 ± 6 beats min^-1 (P < 0.05). Stage II. After a blood loss of 375 (300–500) ml (15 (13–16)%) MAP fell to 62 ± 9 mmHg and HR to 95 ± 5 beats min^-1 (P < 0.05). Stage III. A blood loss of 1113 (825–1450) ml (44 (30–52)%) resulted in a MAP of 50 ± 4 mmHg and an increase in HR to 206 ± 3 beats min^-1 (P < 0.05). Adrenaline increased from 0.3 ± 0.1 to 0.8 ± 0.3 (stage II) and 3.6 ± 1.1 nmol l^-1 (stage III) (P < 0.05); noradrenaline from 0.4 ± 0.1 to 1.5 ± 0.4 (stage II) and 5.9 ± 1.7 nmol l^-1 (stage III) (P < 0.05); PP from 6.2 ± 1.6 to 13.3 ± 2.3 (stage II) and 20.9 ± 7.8 pmol l^-1 (stage III) (P < 0.05). VP changed only marginally, but ALDO increased from 496 ± 54 to 623 ± 76 pmol l^-1 (stage III) (P < 0.05). The results suggest that a high HR and intense sympathetic activity is seen during severe haemorrhage in the pig while vagal slowing of the heart and moderate hypotension are prominent when bleeding amounts to approximately 15% of the estimated blood volume.     

Lactation affects pressor,volumetric and natriuretic responses to angiotensin II in goats

Demands on cardiovascular function and fluid turnover increase during lactation and pregnancy in the goat, but the hormonal status is different. This study is aimed at investigating the effects of hypertensive angiotensin II (ANGII) in lactating goats. The results were compared with those of pregnancy and control conditions. ANGII (0.5 pg min^-1) was infused intravenously for 60 min (n = 6). The rise in blood pressure in response to ANGII was attenuated during lactation as in pregnancy (P < 0.001 vs control period). ANGII caused reflex bradycardia. Plasma protein concentration decreased by 7.5% during infusions in lactating goats (pregnancy: 9%; control period: 4.5%). Renal Na excretion increased by 260% (lactation), by 400% (pregnancy; n.s. vs. lactation), and by 800% (control period; P < 0.01 vs. lactation). The glomerular filtration rate was unchanged during ANGII infusions in lactating animals, but increased in the other periods. Effective renal plasma flow decreased. ANGII raised aldosterone from < 34.5 pmol 1^--¹ to 539 ± 80 pmol l^-1 (lactation) and to 428 ± 41 pmol l^-1 (control; P < 0.05 vs. lactation), and from 72 ± 9 to 651 ± 103 pmol l^-1 (pregnancy; P < 0.01 vs. lactation). Plasma progesterone was undetectable during lactation, but varied from 0 to 17 nmol l^-1 during control conditions and was 16 ± 1 nmol l^-1 during pregnancy. Oestradiol 17β was 181± 22 pmol l^-1 in pregnant goats, and undetectable in lactating animals. In conclusion, lactation affects ANGII-induced changes in cardiovascular and fluid regulation, but in this period the effects were not related to progesterone or oestradiol 17 β.     

Atrial plasma ANP and NH2-terminal proANP during right atrial pressure increase in humans

To compare plasma NT-proANP, a stable and biologically inactive N-terminal portion of ANP prohormone, with the known plasma ANP response to increased right atrial pressure a Swan–Ganz catheter was inserted into the right atrium of five normal healthy male volunteers. The elevation of right atrial pressure was produced by a head-down tilt after a hypertonic saline infusion. Blood samples were drawn from the lumen of the right atrium. After 5 min of starting the tilt the right atrial pressure had increased from 7.0±1.0 to 11.6±0.9 mmHg (P<0.05) and then began to normalize in spite of the constant tilt. Atrial plasma ANP increased in relation to the pressure increase and peaked at 15 min after the start of the tilt. The change was from 27.9±6.5 to 53.9±9.7 pmol L^-1 (P<0.05). Atrial plasma NT-proANP increased significantly from 357±91.2 to 529.1±116.0 pmol L^-1 (P<0.05) at 10 min and remained high throughout the experiment. The molar ratio of NT-proANP to ANP varied in atrial plasma from 9.5±1.2 to 13.9±2.7 showing that the plasma clearance of ANP from plasma was much higher than that of NT-proANP.     

Near-infrared spectrophotometry determined brain oxygenation during fainting

During orthostatic hypotension we evaluated whether presyncopal symptoms relate to a reduced brain oxygenation. Nine subjects performed 50° head-up tilt for 1 h and eight subjects were followed during 2 h of supine rest and during 1 h of 10° head-down tilt. Cerebral perfusion was assessed by transcranial Doppler determined middle cerebral artery blood velocity (MCA v_mean), while brain blood oxygenation was assessed by near-infrared spectrophotometry determined concentration changes for oxygenated (ΔHbO₂) and deoxygenated haemoglobin and brain cell oxygenation by the oxidized cytochrome c concentration (ΔCytO₂). During head-up tilt, six volunteers developed presyncopal symptoms and mean arterial pressure (88 (78–103) to 68 (57–79) mmHg; median and range), heart rate (96 (72–111) to 65 (50–107) beats min^?1), MCA v_mean (59 (51–82) to 41 (29–56) cm s^?1), ΔHbO₂ (by ?5.3 (?3.0 to ?14.8) μmol l^?1) and ΔCytO₂ were reduced (by ?0.2 (?0.1 to ?0.4) μmol l^?1; P < 0.05). During tilt down the cardiovascular variables recovered immediately and ΔHbO₂ increased to 2.2 (?0.9–12.0) mmol L^?1 above the resting value and also ΔCytO₂ recovered. In the nonsyncopal head-up tilted subjects as in the controls, blood pressure, heart rate, MCA v_mean and brain oxygenation indices remained stable. The results suggest that during orthostasis, presyncopal symptoms relate not only to cerebral hypoperfusion but also to reduced brain oxygenation.     

Characterization,localization and actions of endothelins in umbilical vessels and placenta of man

Endothelin-like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin-like immunoreactivity (0.4–1.4 pmol g^-1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin-like immunoreactivity in the amniotic fluid was much higher (77 pmol l^-1) than in umbilical cord plasma (10 pmol l^-1). Characterization by reverse phase HPLC revealed that most of the endothelin-like immunoreactivity eluted in the position of synthetic endothelin-1 or oxidized endothelin-1. Specific, high affinity binding sites for endothelin-1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin-1 and -3 were almost equipotent as competing ligands for endothelin-1 binding sites, whereas in the umbilical artery endothelin-3 was much less potent than endothelin-1. Scatchard analysis of the binding for placental membranes displayed a straight line (r=–0.994) indicating a single class of endothelin receptors with a K_d-value of 80 pmol l^-1 and B_max of 113 fmol mg^-1. Endothelin-1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l^-1 while endothelin-3 had no contractile effect up to 10^-7 mol l^-1. It is concluded that endothelin-1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin-1 was observed in foetal circulation and amniotic fluid. Endothelin-receptors seem to be of different types in placenta (ET_B type) and umbilical vessels (ET_A type).     

Middle cerebral artery blood velocity during rowing

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 ± 3 to 67 ± 5 cm s^?1; mean ± SE) and mean arterial (86 ± 6 to 97 ± 6 mmHg) and central venous pressures (0 ± 2 to 8 ± 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 ± 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 ± 7 cm s^?1 and it was in phase with the highest mean arterial pressure (125 ± 14 mmHg), while the central venous pressure was highest after the stroke (20 ± 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.     

Sympathetic influence on cardiovascular responses to sustained head-up tilt in humans

Sympathetic β-adrenergic influences on cardiovascular responses to 50d? head-up tilt were evaluated with metoprolol (β₁-blockade; 0.29 mg kg^-1) and propranolol (β₁ and β-₂-blockade; 0.28 mg kg^-1) in eight males. A normotensive-tachycardic phase was followed by a hypotensive-bradycardic episode associated with presyncopal symptoms after 23pL3 min (control, mean pLSE). Head-up tilt made thoracic electrical impedance (3.0pL10Ω), mean arterial pressure (MAP, 86pL4-93pL4 mmHg), heart rate (HR, 63pL3-99pL10 beats min^-1) and total peripheral resistance (TPR, 15pL1-28pL4 mmHg min L^-1) increase, while central venous oxygen saturation (74pL2-58pL4%), cardiac output (5.7pL0.1–3.1pL0.3 L min^-1), stroke volume (95pL6-41pL5 mL) and pulse pressure (55pL4-49pL4 mmHg) decreased (P < 0.05). Central venous pressure decreased during head-up tilt (7pL2-0pL1 mmHg), but it remained stable during the sustained tilt. At the appearance of preswyncopal symptoms MAP (49pL3 mmHg), HR (66pL4 beats min^-1) and TPR (15pL3 mmHg min L^-1) decreased (P < 0.05). Neither metoprolol or propranolo changed tilt tolerance or cardiovascular variables, except for HR that remained at 57pL2 (metoprolol) and 55pL3 beats min^-1 (propranolol), and MAP that remained at 87pL5 mmHg during the first phase with metoprolol. In conclusion, sympathetic activation was crucial for the heart rate elevation during normotensive head-up tilt, but not for tilt tolerance or for the associated hypotension and bradycardia.     

Vascular effects of endothelin-1 in the cat; modification by indomethacin and l-NAME

Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol × kg body wt^-1x min^-1for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 ± 4.8 mmHg (n= 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70–80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18–23%. Pre-treatment with indomethacin or a combination of indomethacin and l -NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol × kg body wt^-1x min^-1, caused an increase in MAP of 79 ± 11 mmHg (n= 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60–80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and l -NAME-sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.     

The influence of transmural pressure and longitudinal stretch on K+– and Ca2+–induced coronary artery constriction

The aim of the study was to investigate transmural pressure and longitudinal stretch modulation of K⁺- and Ca²⁺-induced constriction of porcine conductance coronary arteries. In a pressure myograph set-up, left anterior descendent coronary arteries from 70 to 90 kg pigs were investigated at pressures from 20 to 120 mmHg. Longitudinal extension ratio (λ = L/L₀^–1, where L₀ is the in situ length and L the examination length) varied between 0.9 and 1.1. Two protocols were carried out: (1) Outer diameter response to maximal depolarization by K⁺ 125 m M at 20–120 mmHg and λ at 0.90–1.10. (2) Concentration–response curves with K⁺ (4.7–125 m M ) and Ca²⁺ (0.05–4.0 m M ) at four combinations of P and λ (P = 100 mmHg, λ = 0.9; P = 100 mmHg, λ = 1.1; P = 40 mmHg, λ = 0.9; p = 40 mmHg, λ = 1.1). Results: Endothelial function was preserved. A slight (<5% diameter reduction) basal tone and no myogenic response was found. Protocol 1: the constriction to K⁺ 125 m M was maximal in a wide pressure range from 40 to 120 mmHg. Despite the fact that K⁺-induced diameter changes were statistically insignificant between 40 and 120 mmHg, there was a linear trend towards smaller diameter changes in this pressure range (r = –0.54, P < 0.01). Stretch influenced constriction at 20 mmHg because λ = 0.90 and 0.95 resulted in smaller diameter-reductions than λ = 1.00–1.10 (P < 0.05 for all). Contrastingly, at 120 mmHg the constriction at λ = 1.10 was smaller than the responses at λ = 0.90–1.05 (P < 0.05 for all). Protocol 2: EC₅₀ and EC₁₀ values for K⁺- and Ca²⁺ were generally higher (more sensitive) at 40 compared with 100 mmHg. Stretch was of no significant importance for EC₅₀ and EC₁₀ at 40 and 100 mmHg. It is concluded that porcine coronary artery constriction to non-metabolized agonists is maximal at 40 mmHg with a trend towards smaller diameter changes with higher pressures. Longitudinal stretch affects responsiveness at pressure extremes.     

Intra- and extracranial artery blood velocity during a sudden blood pressure decrease in humans

The intra- and extracerebral Doppler artery blood velocity responses to a 10-mmHg abrupt blood pressure (BP) decrease in ten healthy men were studied. This decrease was obtained using two cuffs placed over both thighs. First, cuffs were inflated to pressures greater than the arterial BP for 5 min. Next, they were deflated to 60 mmHg in order to prevent venous return from the legs. We obtained a decrease in mean arterial BP of from 101 (10) to 90 (10) mmHg [mean (SD), P < 0.01] without modifications in the heart rate [HR, 88 (14) beats min⁻¹]. Middle cerebral artery mean blood velocity (MCAmv) decreased immediately from 50 (10) to 42 (12) cm s⁻¹ (P < 0.05). Simultaneously, temporal superficial artery mean blood velocity (TSAmv) decreased from 11 (3) to 7 (2) cm s⁻¹ (P < 0.05) and common carotid artery blood flow (CCAbf ) decreased from 305 (23) to 233 (33) ml min⁻¹ (P < 0.05). After 5 s, MCAmv and CCAbf returned to baseline values, whereas TSAmv [8 (2) cm s⁻¹], mean arterial BP [86 (10) mmHg] remained low and HR increased [92 (12) beats min⁻¹]. TSAmv, BP and HR returned to baseline values in 1 min. These data confirm that cerebral blood flow (CBF) is very rapidly regulated but that blood flow in extracranial territories is not and that it follows the arterial BP changes. Accepted: 8 April 1997     

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans

The effect of intravenous administration of the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1 0.2, 1 and 8 pmol kg^?1 min^?1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95±5 mmHg to 110±6 mmHg (P<0.01) and reduced heart rate from 64±4 beats min^?1 to 58±4 beats min^?1 (P<0.05) at 8 pmol kg^?1 min^?1. Coronary sinus blood flow was reduced maximally by 23±4% (P<0.01) and coronary vascular resistance increased by 48±11% (P<0.01). Coronary sinus oxygen saturation decreased from 35±1% to 22±2% at 2 min after the infusion (P<0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction in coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24±3% over the myocardium (P<0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.     

Atrial natriuretic peptide (ANP): response to NaCI is attenuated in rat atria in vitro after hypophysectomy

The present study documents the effects of hypophysectomy on the NaCl-stimulated release and on the basal secretion rates of ANP from rat atria in vitro. Three weeks before the experiments rats were subjected to hypophysectomy or to a corresponding sham operation. Atria were excised and superfused in an organ bath with a physiological buffer solution (PBS, 294 mosmol kg^-1). After a control period of 5 min, superfusion was made with hyperosmotic NaCI (330 mosmol kg^-1) for 10 min, and then again with PBS, but now for 15 min. Atria were paced with field stimulation (4 Hz, 20 V, 1 ms) and the resting tension was kept at 5 mN. The sham-operated animals responded with a significant increase (P < 0.05) in the secretion rate of ANP (from 137 ± 13 pg ml^-1 [n = 35] to 235 ± 24 [n = 34], means + SE) to the NaCI stimulus. The hypophysectomy blunted the ANP response to hyperosmotic NaCl. In addition, basal secretion rate was signficantly (P < 0.001) lower in the hypophysectomized than in the sham-operated animals during the whole experiment. Gel filtrations revealed that, during the hyperosmotic NaCI, both groups secreted exclusively ANP 1–28. We conclude that hypophysectomy blunts the basal as well as stimulus-induced in-vitro release of ANP from rat atria.     

The hormonal responses to repetitive brief maximal exercise in humans

Summary The responses of nine men and nine women to brief repetitive maximal exercise have been studied. The exercise involved a 6-s sprint on a non-motorised treadmill repeated 10 times with 30 s recovery between each sprint. The total work done during the ten sprints was 37,693±3,956 J by the men and 26,555±4,589 J by the women (M > F,P<0.01). This difference in performance was not associated with higher blood lactate concentrations in the men (13.96± 1.70 mmol·^–1) than the women (13.09±3.04 mmol·l^–1). An 18-fold increase in plasma adrenaline (AD) occurred with the peak concentration observed after five sprints. The peak AD concentration in the men was larger than that seen in the women (9.2 +- 7.3 and 3.7 ± 2.4 nmol · l^–1 respectively,P<0.05). The maximum noradrenaline (NA) concentration occurred after ten sprints in the men (31.6±10.9 nmol·l^–1) and after five sprints in the women (27.4 ± 20.8 nmol · l^–1). Plasma cardiodilatin (CDN) and atrial natriuretic peptide (ANP) concentrations were elevated in response to the exercise. The peak ANP concentration occurred immediately postexercise and the response of the women (10.8 ± 4.5 pmol · l^–1 was greater than that of the men (5.1 ± 2.6 pmol · l^–1,P<0.05). The peak CDN concentrations were 163 ± 61 pmol · l^–1 for the women and 135 ± 61 pmol · l^–1 for the men. No increases in calcitonin gene related peptide (CGRP) were detected in response to the exercise. These results indicate differences between men and women in performance and hormonal responses. There was no evidence for a role of CGRP in the control of the cardiovascular system after brief intermittent maximal exercise.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n= 6). ANP (2 μrg min^-1), ANGII (0.5 μg min^-1), or ANGII + ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5–10 mmHg both in pregnancy and in non-pregnancy. When ANGII + ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 μmol min^-1in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 μmol min^-1in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Effects of angiotensin ll on blood flow in rat submandibular gland

The effect of angiotensin II (Ang II) was studied on blood flow in the submandibular gland and tongue in male rats. Blood flow changes were determined with laser Doppler flowmetry and Ang II was infused into the common carotid artery before and after i.v. doses (18 nmol kg^-l) of the angiotensin II antagonist saralasin. Angiotensin II (10–60 pmol min^-l) dose-dependently increased blood pressure and tongue blood flow, whereas glandular blood flow decreased at all of the doses used. After saralasin administration the angiotensin II effects on blood pressure, tongue and glandular blood flow were significantly diminished (glandular blood flow reduction was diminished from 29%-3%, P < 0.005, n = 9). However, the responsiveness of these 3 parameters to local infusions with noradrenaline (0.75–3.0 pmol min^-1) was unaffected by saralasin. The dose of saralasin used in the present study did not affect any of the parameters on it's own. Our results show that vascular receptors sensitive to angiotensin II operate in the submandibular gland but not in the tongue.     

Fluid balance in patients with chronic renal failure assessed with N‐terminal proatrial natriuretic peptide,atrial natriuretic peptide and ultrasonography

The N‐terminal proatrial natriuretic peptide (proANP) has become an important parameter for assessing the prognosis of patients with cardiac disease. Its use for evaluating the hydration status in patients with chronic renal failure, however, is still under investigation. The present study comprised 12 haemodialysis (HD) and 17 pre‐dialysis patients. In the HD patients, the inferior vena cava diameter during quiet expiration (IVCe) was estimated by ultrasonography and plasma concentrations of N‐terminal proANP, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) were measured before and 4 h after termination of HD. In the pre‐dialysis patients venous blood samples were taken during rest to measure plasma N‐terminal proANP and ANP and serum creatinine. Normal values for N‐terminal proANP and ANP were obtained from 18 healthy volunteers. The plasma concentrations of N‐terminal proANP and ANP in healthy volunteers were 328 ± 92 and 11.4.0 ± 3.1 p M L^?1, respectively. In pre‐dialysis patients, serum creatinine ranged from 110 to 447 μM L^?1 and was significantly correlated to plasma N‐terminal proANP (r=0.60, P < 0.05) but not to ANP. This may indicate that N‐terminal proANP is more dependent on renal function for its clearance than ANP, which is probably cleared by extrarenal mechanisms as well. In HD patients, IVCe was significantly correlated to the three hormones before HD, most strongly to N‐terminal proANP. After dialysis, IVCe was significantly correlated to ANP and cGMP but was not correlated to N‐terminal proANP. This may suggest that proANP takes a longer time than other hormones to reflect changes in intravascular volume. In conclusion, N‐terminal proANP is a hormone closely related to degree of renal function. Furthermore, it is a sensitive marker reflecting the interdialytic hydration status in HD patients, as indicated by its high correlation to IVCe, a standard method which is used frequently nowadays to assess the body hydration. However N‐terminal proANP could not reflect the acute changes in fluid volume induced by HD, probably because it is slowly metabolized.     

Plasma immunoreactive atrial natriuretic peptide and vasopressin after ethanol intake in man

To study the mechanisms of alcohol-induced diuresis, the plasma concentration of immunoreactive atrial natriuretic peptide and arginine vasopressin, serum sodium and osmolality, plasma renin activity and aldosterone, urinary sodium and volume, free water clearance, blood pressure and heart rate were measured in seven healthy men after oral intake of ethanol (1.5 g kg^-1 in 6 h). Serum ethanol levels increased to 27 ± 4 mmol 1^-l (mean ± SD) in 30 min and remained detectable for 14 h. Serum osmolality rose from 280±10 to 340 ± 4 mosm kg^-1 in 2 hours (P < 0.01) and was 300 ± 4 at 14 h (P < 0.01). Formation of hypotonic urine began after the alcohol intake and resulted in a net loss of 0.9 ± 0.1 kg water in 2 h. Free water clearance increased from -3.4 ± 1.4 to 2.8 ± 1.5ml min^-l in 2 h (P < 0.01). Plasma immunoreactive arginine vasopressin decreased from 5.7 ± 2.1 to 3.3 ± 1.3 ng 1^-1 (P = 0.05) in 30 min and increased to 17 ± 25 and 12±10 ng 1^-1 at 6 and 12 h, respectively (P < 0.05 for both). Plasma immunoreactive atrial natriuretic peptide levels decreased from 17 ± 9 to the minimum of 11 ± 3 ng 1^-1 in 2 h (P < 0.01) and returned to the initial levels in 6 h. Serum sodium, plasma renin activity and plasma aldosterone increased maximally by 4 ± 2 , 165 ± 153 and 143 ± 101 % (P < 0.01 each) during 1–6 h. No changes in blood pressure were observed during the ingestion period, but the heart rate rose significantly from 70 min^-1 at 6 p.m. to 95 min^-1 at 12 p.m. We conclude that ethanol intake in relation to serum ethanol levels caused in the first phase a rapid increase in osmolality which was associated with a decrease in plasma immunoreactive arginine vasopressin. This caused hypotonic diuresis and increased free water clearance followed by volume contraction which evidently led to decreased plasma immunoreactive atrial natriuretic peptide. Serum osmolality was significantly elevated during the whole experiment and serum sodium 1–2 h after the ethanol intake. This was associated with the return of plasma immunoreactive atrial natriuretic peptide to initial levels after 6 h, the increase in plasma immunoreactive arginine vasopressin levels and reduced diuresis after 2 h. Our results suggest that ANP is not responsible for the diuresis seen after the alcohol intake.     

Myocardial interstitial noradrenaline monitoring during occlusion of inferior vena cava in cats

To investigate myocardial interstitial noradrenaline (NA) kinetics during activation of systemic sympathetic nerves, we applied a dialysis technique to the left ventricle of anaesthetised cats and monitored myocardial interstitial NA levels during 6-min occlusion of the inferior vena cava (IVC). Dialysis probes were implanted in the left ventricular wall, and dialysate NA levels as an index of myocardial interstitial NA levels, were measured with high-performance liquid chromatographic–electrochemical detection. During IVC occlusion, dialysate NA levels progressively increased from 110 ± 17 pmol L^?1 in the control and reached 620 ± 160 pmol L^?1 at 4–6 min of IVC occlusion. Local administration of ω-conotoxin GVIA at 10 μM decreased the control dialysate NA level to 35 ± 0.2 pmol L^?1. The IVC occlusion induced increase in dialysate NA was suppressed only at 0–2 min of IVC occlusion. Intravenous injection of ω-conotoxin GVIA (10 μg kg^?1) did not increase the dialysate NA levels during IVC occlusion. Local administration of desipramine at 100 μM increased the control dialysate NA level to 900 ± 73 pmol L^?1. The IVC occlusion induced progressive increase in dialysate NA was augmented at 2–6 min of IVC occlusion. These results suggest that the early increase in myocardial interstitial NA levels is mainly caused by neuronal release of NA from cardiac sympathetic nerve terminals, and that extraction from the circulation and neuronal NA uptake contribute to changes in myocardial interstitial NA levels after a delay of several minutes.     

Transmural distribution of biochemical markers of total protein and collagen synthesis,myocardial contraction speed and capillary density in the rat left ventricle in angiotensin ll-induced hypertension

The effect of angiotensin II-induced hypertension on selected biochemical parameters was studied in Sprague-Dawley rats. Angiotensin II infusion at rates of 41.7 μg h^-1 kg^-1 and 12.5 μg h^-1 kg^-1 for 2, 5, 10 and 15 days elevated the systolic blood pressure from 143 ± 7 mmHg to 215–230 mmHg (P < 0.001) and 185–195 mmHg (P < 0.001), respectively. The left ventricular weight/body weight ratio increased 10–14% (P < 0.05) and 23–32% (P < 0.001) after 2–15 days in rats treated at the lower and higher infusion rates, respectively. Prolyl 4-hydroxylase (PH) activity, a marker of collagen synthesis, was evenly distributed in the left ventricle. PH activity increased by about 100% in both subendocardial and subepicardial layers of the left ventricular wall after angiotensin II infusion for 10 days at 41.7 γ h^-1 kg^-1, but remained unaltered at 12.5 μg h^-1 kg^-1. No change was observed in hydroxyproline concentration. Myosin isoenzymes (V₁-V₃), which reflect myocardial contractility, were unevenly distributed in the left ventricular wall: the proportion of the fast-turnover isoenzyme (V₁) was smaller in the subendocardial layer than in the subepicardial layer. The proportion of V_l decreased after treatment in both layers. Alkaline phosphatase activity, a marker of capillary density, was evenly distributed transmurally in the left ventricular wall. Angiotensin II caused a slight decrease in this activity in both myocardial layers. The results suggest that the elevation of blood pressure leads to transmurally evenly distributed changes in biochemical parameters reflecting collagen synthesis, capillary density and contractile properties of the myocardium.     

Nitric oxide and the role of blood pressure variability to the kidney

Blood pressure variability is buffered by at least two mechanisms: the arterial baroreceptor reflex and nitric oxide (NO). Only recently is the importance of blood pressure variations on cardiovascular control being investigated. Here we report of a study performed in conscious dogs, in which renovascular hypertension was induced. Reduction of renal arterial pressure (RAP) to 85 mmHg for 24 h elicited profound hypertension by 60 mmHg (vs. control: 110 ± 3 mmHg; P < 0.01). This was accompanied by reduced volume and sodium excretion (–48% of control, P < 0.01 and –80% of control, P < 0.01, respectively) and augmented renin release by more than two‐fold (P < 0.01). This intervention was compared with a protocol in which RAP was reduced to the same mean value, however, RAP oscillated by ±10 mmHg at 0.1 Hz. This manoeuvre led to a transient increase in NO₃ excretion in urine (P < 0.01), blunted antidiuresis (–14% of control) as well as antinatriuresis (–40% of control) and attenuated the increased renin release by 30% (P < 0.05). In consequence, the magnitude of blood pressure increase was only half as high as that observed during static reduction of RAP (P < 0.01). It is concluded that blood pressure oscillations to the kidney have a profound influence on water and electrolyte balance and on renin release, which alleviates the onset of Goldblatt hypertension.