Lymphatic transport of cellular enzymes from muscle into the intravascular compartment.

In an experimental study, employing anaesthetized dogs, it was investigated whether cellular enzymes from peripheral skeletal muscle get into the circulating blood by diffusion across capillary membranes or by lymphatic transport. In the experimental group 1, the animals were anaesthetized only. The plasma activities of the four enzymes measured--lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatine kinase--did not show any mentionable change during a time period of 6 h. In group 2 one hind limb of each animal was moved passively for 1 h. Alanine aminotransferase remained unchanged in plasma, the activities of the three other enzymes increased significantly. In group 3 one hind limb was made hypoxic by clamping the femoral blood vessels for 1 h. No activity changes were observed. When the period of hypoxia was followed by a 1-hour period of passive movement in group 4, the alterations in plasma activities were almost identical to those observed in group 2. In group 5 the experimental procedure was as in group 4, in addition the lymph from the thoracic duct was quantitatively withdrawn. The enzyme activities in plasma revealed a tendency to decrease rather than increase. Lymph flow increased significantly as well as the lymphatic activities of those enzymes which have high intracellular activities in muscle. The results prove, that enzymes from muscle are transported from the interstitial into the intravascular compartment mainly by lymphatic transport. Indications were found that the interruption of blood flow in one hind limb did not result in an enzyme release from muscle cells. It is discussed how changes in lymph flow, occurring during physical exercise for example, affect enzyme activities in plasma.     

Stimulation of rapidly adapting pulmonary stretch receptors by pulmonary lymphatic obstruction in dogs

The effects of pulmonary lymphatic obstruction and pulmonary venous congestion on the activities of slowly adapting receptors (SAR) and rapidly adapting receptors (RAR) of the airways were examined in anaesthetized, artificially ventilated dogs. In 11 out of 12 RAR (12 dogs) examined, pulmonary lymphatic obstruction for a period of 20 min produced a sustained significant increase in activity without a significant change in peak airway pressure and dynamic compliance. The activity remained significantly elevated even after the pulmonary lymphatic obstruction was released. This stimulus was without effect on the SAR (n = 5 dogs). Pulmonary venous congestion alone increased the RAR activity (n = 7 dogs) significantly without producing significant changes in airway mechanics. Lymphatic obstruction, when superimposed upon congestion, did not produce a further significant increase in activity. In four dogs the effect of pulmonary venous congestion (left atrial pressure increased from 7.6 +/- 1.7 to 16.3 +/- 2.7 mmHg) (1 mmHg = 133.3 Pa) on pulmonary lymphatic flow was examined. The procedure caused a significant increase in lymph flow. These results suggest that in the dog, the RAR activity is influenced by changes in the pulmonary extravascular space.     

Evaluating flux of labeled albumin into the pulmonary interstitium of sheep lungs.

A noninvasive method was used to measure the movement of 131I-labeled albumin across the pulmonary microvascular barrier of a blood-perfused in situ sheep lung lymph preparation. After injection of labeled albumin into the blood, external measurements of gamma activity were taken for 2 h. The interstitial concentrations were calculated by applying the external activities and sampled lung lymph concentrations to a mass transport model. For the external activities and lymph activities to yield the same quantitative results, two modifications were necessary. First, lymph concentrations were corrected for transport delay from the lymphatic system. Second, externally detected radioactivity had to be corrected for the contribution of unbound nuclide. Application of a mathematical model to the data indicated the extravascular distribution volume for albumin was 79% of the pulmonary blood volume, and the extravascular distribution volume for radiolabeled iodide was 4.42 times greater than the pulmonary blood volume. The permeability-surface area product for iodide in the lung was estimated to be 0.274 ml.min-1.g blood-free dry lung wt-1. The transport delay in the lymphatic system was approximately 30-45 min and represented a volume of 1.44-2.80 ml.     

Comparative effects of cardiac receptors and sinoaortic baroreceptors on elevations of plasma vasopressin and renin activity elicited by haemorrhage

Increases in plasma vasopressin and renin activity that occur in response to haemorrhage have been attributed in part to reflex effects from cardiac receptors and sinoaortic baroreceptors, but the relative importance of these different receptors in causing humoral changes during haemorrhage in conscious dogs has not been reported. We investigated this question by hemorrhaging 6 sham-operated (SO), 6 cardiac-denervated (CD), 4 sinoaortic-denervated (SAD), and 4 combined sinoaortic and cardiac-denervated (SACD), conscious dogs. Blood was removed at a rate of 0.9 ml/kg X min. Plasma vasopressin and renin samples were taken during a control period and after 10, 20, and 30 ml/kg of blood had been removed. Results (mean +/- SE) are shown in the tables below. (table; see text) These experiments illustrate that: resting plasma levels of vasopressin and renin in conscious dogs are unaffected by the denervation procedures used in these experiments, the increase in plasma vasopressin that occurs during haemorrhage is mediated largely via cardiac receptors, with a considerably smaller contribution from the sinoaortic baroreceptors, during moderately severe haemorrhage (30 ml/kg) vasopressin secretion can be increased by a mechanism independent of sinoaortic and cardiac reflexes, the increase in plasma renin activity that occurs during haemorrhage is not dependent upon either cardiac or sinoaortic reflexes.     

Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships

Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Maximum coronary blood flow and minimum coronary resistance in exercise-trained dogs

Exercise training has been found to increase coronary vascularity of the heart in experimental animals. Maximum coronary flow and minimum coronary resistance were determined in 16 dogs with the injection of microspheres (15 micron) into the left atrium at rest and during the intravenous infusion of adenosine (0.7 mg X min-1 X kg-1). Heart rate was paced at 150 beats/min. Dogs were divided into three groups with microsphere injections made before and after 4-5 wk of daily exercise (group 1); before and after 8-10 wk of daily exercise (group II); and before and after 8-10 wk of cage rest (group III). Results of average left ventricular maximum myocardial flow before and after daily exercise were 4.08 +/- 0.34 and 4.89 +/- 0.33 ml X min-1 X g-1 for group I, 5.13 +/- 0.32 and 5.55 +/- 0.56 ml X min-1 X g-1 for group II, and 5.24 +/- 0.43 and 4.34 +/- 0.55 ml X min-1 X g-1 for group III. Arterial pressure, maximum coronary flow, and minimum coronary resistance were not significantly different before and after any condition in all three groups of dogs. Peak reactive hyperemia coronary flow was not altered by daily exercise. These results indicate that maximum coronary flow and minimum coronary resistance were not altered by either 4-5 or 8-10 wk of exercise training.     

Calcium antagonist verapamil inhibits adenosine-induced renal vasoconstriction in the dog

Calcium-dependence of the adenosine-induced renal vasoconstriction was studied in dogs anaesthetized with pentobarbital. Close intraarterial (i.a.) infusion of adenosine (40 and 100 micrograms X min-1) elicited a significant blood flow decrease followed by partial recovery during the 2 min infusion periods as measured with an electromagnetic flow probe. I.a. infusion of verapamil (100 micrograms X min-1) blocked the constrictor response. Verapamil also reduced the vasoconstriction produced by i.a. angiotensin II (0.1 micrograms X min-1) or adrenaline (0.6 micrograms X min-1). Blood pressure remained unchanged throughout all the interventions. The results indicate that the adenosine-induced renal vascular response depends on the availability of extracellular Ca2+ to the contractile mechanism of smooth muscle, a property shared by other well known renal constrictor agents.     

Pulmonary vascular responses to angiotensin II and captopril in conscious dogs

Our objectives were to investigate the extent to which angiotensin II (ANG II) and converting-enzyme inhibition (CEI) exert a direct vasoactive influence on the pulmonary circulation of conscious dogs. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. The effects of ANG II infusion (60 ng X kg-1 X min-1, iv) and CEI with captopril (1 mg/kg plus 1 mg X kg-1 X h-1, iv) on pulmonary vascular P/Q plots were assessed first with the conscious dogs intact and again after combined administration of pharmacological antagonists to block sympathetic alpha- and beta-adrenergic, cholinergic, and arginine vasopressin receptors. In intact dogs, ANG II increased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure, PAP-PCWP) over the entire range of Q studied (60-120 ml X min-1 X kg-1). Conversely, CEI decreased (P less than 0.05) PAP-PCWP at each level of Q. After administration of the autonomic nervous system and arginine vasopressin receptor antagonists, ANG II again increased (P less than 0.01) and CEI decreased (P less than 0.01) PAP-PCWP over the entire range of Q studied. Thus exogenous administration of ANG II results in active, nonflow-dependent constriction of the pulmonary circulation, and this effect is not dependent on the autonomic nervous system or increased circulating levels of arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dipyridamole and furosemide on renal function during adenine dinucleotide infusion in rats

In anaesthetized rats kept on normal diet an i.v. infusion of NAD (200 nmole X kg-1 X X min-1) induced a decrease in renal plasma flow (CPAH), glomerular filtration rate (GFR) and electrolyte excretion accompanied by an increase in plasma adenosine concentration. Separate infusions of a small dose of NAD (50 nmole X kg-1 X min-1) or dipyridamole (25 micrograms X kg-1 X min-1) did not affect renal function or plasma adenosine concentration. However, when the above small doses of both agents were given simultaneously, GFR, CPAH and electrolyte excretion fell significantly, indicating potentiation of NAD action by dipyridamole, associated with increased plasma adenosine level. An i.v. infusion of furosemide failed to abolish the depression of renal function in response to NAD. The data suggest that the causal factor of this depression was adenosine and not NAD itself.     

Effects of contraction frequency and duty cycle on diaphragmatic blood flow

The effects of diaphragmatic contraction frequency (no. of intermittent tetanic contractions/min) at a given tension-time index and of duty cycle (contraction time/total cycle time) on diaphragmatic blood flow were measured in anesthetized mongrel dogs during bilateral supramaximal phrenic nerve stimulation. Diaphragmatic blood flow was measured by the radionuclide-labeled microsphere method. Contraction frequency was varied between 10 and 160/min at duty cycles of 0.25 and 0.75. Diaphragmatic blood flow increased with contraction frequency from 1.47 +/- 0.13 ml X min-1 X g-1 (mean +/- SE) at an average of 18/min to 2.65 +/- 0.16 ml X min-1 X g-1 at 74/min (P less than 0.01) with a duty cycle of 0.25 and from 1.32 +/- 0.19 ml X min-1 X g-1 at an average of 15/min to 1.96 +/- 0.15 ml X min-1 X g-1 at 80/min (P less than 0.02) with a duty cycle of 0.75. At higher contraction frequencies diaphragmatic blood flow did not increase further at both duty cycles. In addition, diaphragmatic blood flow was higher with a duty cycle of 0.25 than 0.75 at all contraction frequencies. We conclude that frequency of contraction is a major determinant of diaphragmatic blood flow and that high duty cycle impedes diaphragmatic blood flow.     

Increased oxygen consumption associated with breathing activity in fetal lambs

To examine the relationship between fetal O2 consumption and fetal breathing movements, we measured O2 consumption, umbilical blood flow, and cardiovascular and blood gas data before, during, and after fetal breathing movements in conscious chronically catheterized fetal lambs. During fetal breathing movements, O2 consumption increased by 30% from a control value of 7.7 +/- 0.7 (SE) ml X min-1 X kg-1. Umbilical blood flow was 210 +/- 21 ml X min-1 X kg-1 before fetal breathing movements; in 9 of 16 samples it increased by 52 +/- 12 ml X min-1 X kg-1, while in the other 7 it decreased by 23 +/- 9 ml X min-1 X kg-1. Umbilical arterial and venous O2 partial pressures and pH fell during fetal breathing movements, and the fall was greater when umbilical blood flow was decreased. Partial CO2 pressure rose in both vessels, and again the increase was greatest when umbilical blood flow fell during fetal breathing movements. Also associated with a fall in umbilical blood flow was the transition from low-amplitude irregular to large-amplitude regular fetal breathing movements. It is concluded that fetal breathing movements increase fetal O2 demands and are associated with a transient deterioration in fetal blood gas status, which is most severe during large-amplitude breathing movements.     

Assessment of coagulation cascade during air microembolization of the lung

Experiments were performed to determine whether activation of the coagulation cascade was required for pulmonary vascular permeability to increase during microembolization of the lung. For 30-45 min air microemboli were intravenously infused (0.05-0.10 ml X kg-1 X min-1) into awake sheep with chronic lung-lymph fistulas and anesthetized mongrel dogs. During embolization the pulmonary arterial pressure increased, and O2 partial pressure (PaO2) fell by more than 20 Torr (P less than 0.01). Subsequently lymph flow nearly tripled without a change in the lymph-to-plasma protein concentration ratio. Partial thromboplastin and prothrombin times, biological activity of antithrombin III, and circulating concentration of 125I-labeled dog or sheep fibrinogen did not change during or following air infusion. In two additional sheep an intravenous infusion of thrombin at 0.6 U X kg-1 X min-1 for 15 min resulted in a 20% decrease in 125I-labeled sheep fibrinogen concentration without a change in pulmonary arterial pressure or PaO2. We conclude that air microembolization can increase permeability to water and protein without a detectable activation of the coagulation cascade in the sheep or dog.     

Thoracic duct lymph flow: a comparative study in newborn and adult sheep

To understand better developmental changes in body fluid dynamics, we studied thoracic duct lymph flow in 9 newborn and 5 adult sheep. The experiments were carried out under general anaesthesia following bilateral ligation of the renal vessels and ureters. After a 30 min control period, we administered three successive 5-min intravenous infusions of isotonic saline equivalent to 2% of body weight each, at 30-min intervals. The average basal lymph flow rate was 0.157 +/- 0.033 (SEM) ml.min-1.kg-1 and 0.046 +/- 0.018 ml.min-1.kg-1 in newborns and adults respectively (p less than 0.05). Fluid overloading resulted into similar intravascular retentions at the end of each 30-min period in both groups although the increase in lymph flow was repeatedly more than three times higher in the newborns. The more pronounced lymph flow response in the newborns could not be accounted for only on the basis of a difference in capillary filtration. We speculate that interstitial forces and/or the lymphatic pumping activity play a greater role in facilitating fluid movements in the newborn lamb than in the adult ewe. Overall, the higher capacity of the newborn to eliminate excess interstitial fluid constitutes a significant factor in the body's defense against oedema.     

Effect of regular voluntary exercise on resting cardiovascular responses in SHR and WKY pregnant rats.

The purpose of this study was to assess the influence of regular voluntary exercise in pregnant normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats on 1) uteroplacental perfusion and mean arterial pressure in the resting conscious condition and 2) fetal number, fetal weight, and number of fetal resorptions. WKYs and SHRs were randomly assigned to standard cages [CWKY (n = 10); CSHR (n = 6)] or cages with activity wheels [EWKY (n = 7); ESHR (n = 8)]. EWKYs and ESHRs exercised for 12 wk, and then all rats were bred and experiments were conducted on gestational day 17. Resting blood flow (microspheres), heart rate (HR), and mean arterial pressure (Pa) were measured. No significant difference was found in Pa, HR, uterine blood flow (ESHRs 52 +/- 8 ml.min-1.100 g-1; CSHRs 28 +/- 6 ml.min-1.100 g-1), or maternal placental blood flow (ESHRs, 122 +/- 31 ml.min-1.100 g-1; CSHRs 78 +/- 21 ml.min-1.100 g-1) among the groups. Exercise altered the relationship between maternal placental and uterine blood flow and Pa in the SHR; SHRs with lower Pa maintained higher placental and uterine blood flow after training. Before gestation ESHRs ran on average more kilometers per week than EWKYs (43 +/- 3 vs. 34 +/- 4), but during gestation ESHRs averaged fewer kilometers per week than EWKYs (16 +/- 4 vs. 22 +/- 4). Succinate dehydrogenase activity was higher in the white vastus lateralis (1.02 +/- 0.2 mumol cytochrome c reduced.min-1.g wet wt-1) and vastus intermedius (3.1 +/- 0.5 mumol cytochrome c reduced.min-1.g wet wt-1) muscles of ESHRs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise, dobutamine, and combined atropine, norepinephrine, and epinephrine compared

We compared the cardiovascular effects evoked in conscious dogs by 1) submaximal exercise; 2) infusion of dobutamine (40 micrograms X kg-1 X min-1); and 3) infusion of a combination of atropine (0.15 mg/kg), norepinephrine (0.19 micrograms X kg-1 X min-1), and epinephrine (0.05 micrograms X kg-1 X min-1). Myocardial O2 demand, as estimated by the double product (heart rate X systolic blood pressure), was similar during all three interventions. Cardiac output and heart rate increased significantly (P less than 0.05) during each of the three interventions. Arteriovenous O2 difference and total body O2 consumption, however, increased only during submaximal exercise. Although myocardial blood flow increased similarly during each of the three interventions, blood flow to skeletal muscle and the tongue increased only during exercise. Exercise and the combined infusion of atropine, norepinephrine, and epinephrine produced similar increases in blood flow to the diaphragm and similar decreases in blood flow to the stomach. These changes in blood flow were associated with appropriate changes in vascular resistance. Additionally, blood flow to the brain, kidney, adrenal glands, liver, and intestine did not change during any of the three interventions. Thus, in dogs, submaximal exercise, infusion of dobutamine, and infusion of a combination of atropine, norepinephrine, and epinephrine to evoke a given level of estimated myocardial O2 consumption produce similar increases in cardiac output, heart rate, and myocardial blood flow. In contrast, the changes in total body O2 consumption, arteriovenous O2 difference, regional blood flow, and regional vascular resistance that occur during each of these three interventions are different.     

Collateral sources of costal and crural diaphragmatic blood flow

We measured the contribution of aortic, internal mammary, and intercostal arteries to the blood flow to the costal and crural segments of the diaphragm and other respiratory muscles in seven dogs breathing against a fixed inspiratory elastic load. We used radiolabeled microspheres to measure the blood flow with control circulation, occlusion of the aorta distal to the left subclavian artery, combined occlusion of the aorta and both internal mammary arteries, and occlusion of internal mammary arteries alone. With occlusion of the aorta distal to the left subclavian artery, blood flow to the crural diaphragm decreased from 40.3 to 23.5 ml . min-1 X 100 g-1, whereas costal flow did not change significantly (from 41.7 to 38.1 ml . min-1 . 100 g-1). Blood flows to the sternomastoid and scalene muscles (above the occlusion) increased by 200 and 340%, respectively, whereas flows to the other respiratory muscles did not change significantly. Blood flows to organs above the occlusion either remained unchanged or increased, whereas flows to those below the occlusion all decreased. When the internal mammary artery was also occluded, flows to the crural segment decreased further to 12.1 and costal flow decreased to 20.4 ml X min-1 X 100 g-1. Internal mammary arterial occlusion alone in two dogs had no effect on diaphragmatic flow. In conclusion, intercostal collateral vessels are capable of supplying a significant proportion of blood flow to both segments of the diaphragm but the costal segment is better served than the crural segment.     

Effect of short-term energy intake level and exercise on oxygen consumption in men

The influence of short-term energy intake and cycle exercise on oxygen consumption in response to a 1.5 MJ test meal was investigated in ten young, adult men. On the morning after a previous day's "low-energy" intake (LE regimen) of 4.5 MJ, the mean resting oxygen consumption increased by 0.7 ml X kg-1 X min-1 after the test meal (P less than 0.025). After a "high-energy" intake (HE regimen) of 18.1 MJ, the resting measurement was unchanged (+0.4 ml X kg-1 X min-1) after the meal (n.s.). These trends are the reverse of what would be expected if oxygen consumption in response to feeding is a factor in the acute control of body weight. The mean fasting oxygen consumption during cycle exercise at 56% of VO2max (constant work) for both LE and HE prior intakes was not different at 31.1 ml X kg-1 X min-1. Oxygen consumption during exercise increased after feeding by 0.5 ml X kg-1 X min-1 on the LE regimen (n.s.) and decreased by 1.2 ml X kg-1 X min-1 on the HE regimen (n.s.). These results are also the reverse of what would be expected if oxygen consumption in response to exercise is related to short-term energy intake.     

Abdominal lymphatic pump treatment increases leukocyte count and flux in thoracic duct lymph

BACKGROUND: Previous studies suggest that rhythmic compression of the abdomen (abdominal lymphatic pump techniques, LPT) enhances immunity and resistance to infectious disease, but direct evidence of this has not been documented. In this study, the thoracic duct of eight anesthetized mongrel dogs was catheterized, so the immediate effects of LPT on lymph flow and leukocyte output could be measured. METHODS AND RESULTS: Lymph flow was measured by timed collection or ultrasonic flowmeter, and lymph was collected over ice under 1) resting (baseline) conditions, and 2) during application of LPT. The baseline leukocyte count was 4.8 +/- 1.7 x 10(6) cells/ml of lymph, and LPT significantly increased leukocytes to 11.8 +/- 3.6 x 10(6) cells/ml. Flow cytometry and differential cell staining revealed that numbers of macrophages, neutrophils, total lymphocytes, T cells and B cells were similarly increased during LPT. Furthermore, LPT significantly enhanced lymph flow from 1.13 +/- 0.44 ml/min to 4.14 +/- 1.29 ml/min. Leukocyte flux, computed from the product of lymph flow and cell count, was increased by LPT from 8.2 +/- 4.1 x 10(6) to 60 +/- 25 x 10(6) total cells/min. Similar trends were observed in macrophages, neutrophils, total lymphocytes, T cells and B cells during LPT. CONCLUSIONS: LPT significantly increased both thoracic duct lymph flow and leukocyte count, so lymph leukocyte flux was markedly enhanced. Increased mobilization of immune cells is likely and important mechanism responsible for the enhanced immunity and recovery from infection of patients treated with LPT.     

Effects of different angiotensins during acute,double blockade of the renin system in conscious dogs

Evidence of biological activity of fragments of ANG II is accumulating. Fragments considered being inactive degradation products might mediate actions previously attributed to ANG II. The study aimed to determine whether angiotensin fragments exert biological activity when administered in amounts equimolar to physiological doses of ANG II. Cardiovascular, endocrine, and renal effects of ANG II, ANG III, ANG IV, and ANG-(1-7) (6 pmol.kg-1.min-1) were investigated in conscious dogs during acute inhibition of angiotensin I-converting enzyme (enalaprilate) and aldosterone (canrenoate). Furthermore, ANG III was investigated by step-up infusion (30 and 150 pmol.kg-1.min-1). Arterial plasma concentrations [ANG immunoreactivity (IR)] were determined by an ANG II antibody cross-reacting with ANG III and ANG IV. Metabolic clearance rates were higher for ANG III and ANG IV (391 +/- 19 and 274 +/- 13 ml.kg-1.min-1, respectively) than for ANG II (107 +/- 13 ml.kg-1.min-1). ANG II increased ANG IR by 60 +/- 7 pmol/ml, blood pressure by 30%, increased plasma aldosterone markedly (to 345 +/- 72 pg/ml), and plasma vasopressin transiently, while reducing glomerular filtration rate (40 +/- 2 to 33 +/- 2 ml/min), sodium excretion (50 +/- 7 to 16 +/- 4 micromol/min), and urine flow. Equimolar amounts of ANG III induced similar antinatriuresis (57 +/- 8 to 19 +/- 3 micromol/min) and aldosterone secretion (to 268 +/- 71 pg/ml) at much lower ANG IR increments ( approximately 1/7) without affecting blood pressure, vasopressin, or glomerular filtration rate. The effects of ANG III exhibited complex dose-response relations. ANG IV and ANG-(1-7) were ineffective. It is concluded that 1) plasma clearances of ANG III and ANG IV are higher than those of ANG II; 2) ANG III is more potent than ANG II in eliciting immediate sodium and potassium retention, as well as aldosterone secretion, particularly at low concentrations; and 3) the complexity of the ANG III dose-response relationships provides indirect evidence that several effector mechanisms are involved.     

Atriopeptin alters the vasopressin and renin responses elicited by hemorrhage

This study was designed to investigate whether an infusion of atrial peptide is capable of modulating the hormonal and hemodynamic responses elicited by acute hemorrhage. Conscious dogs were bled at a rate of 0.8 ml.kg-1.min-1 until 20 ml of blood/kg body wt had been removed. Two experiments were performed on each dog; in one experiment the animal was given alpha-human atrial natriuretic peptide (alpha-hANP) (50 ng.kg-1.min-1) dissolved in saline; in the other only the saline vehicle was given. Right and left atrial pressures decreased during hemorrhage in all experiments; the absolute decreases were greater when the animals received atriopeptin, but the differences between treatments were statistically significant only for right atrial pressure. Cardiac output decreased (P less than 0.05) and total peripheral resistance increased (P less than 0.05) during hemorrhage when atriopeptin was infused; although these variables showed similar trends when vehicle alone was infused during hemorrhage, no significant changes occurred. Infusion of atrial peptide did not affect the decrease in arterial blood pressure that occurred during hemorrhage. The increase in plasma vasopressin induced by hemorrhage was potentiated, but the increase in plasma renin activity was attenuated when alpha-hANP was infused. Hemorrhage increased circulating aldosterone levels in each experiment, but the response was less pronounced when alpha-hANP was given during the experiment. Intravenous administration of alpha-hANP modulates the hemodynamic responses elicited by hemorrhage, potentiates the rise in plasma vasopressin, and attenuates the rise in plasma renin activity induced by acute blood loss in conscious dogs.