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PubMed1977

Quantitative structural study of pulmonary circulation in the newborn with aortic atresia, stenosis, or coarctation.

Study of the structural features of the pulmonary circulation in various types of congenital heart disease makes it possible to correlate function and structure in the fetal and newborn lung. We applied quantitative morphometric techniques to the injected and inflated lungs of newborn infants who had died with obstruction to left ventricular outflow from aortic atresia, stenosis, or coarctation. The structure and development of the pulmonary circulation was judged by the number of arteries and veins and their size and wall structure, with particular attention to vessels within the respiratory unit. The study established for the first time that the structure of the pulmonary circulation is modified by the antenatal abnormalities in blood flow that occur through the heart and great vessels in the presence of congenital heart disease. Fetal multiplication of intra-acinar arteries in aortic atresia and stenosis is increased as also is the muscularity of both pre- and intra-acinar arteries and veins, muscle extending into smaller and more peripheral vessels than is normal at birth. When the pulmonary circulation is normal before birth but arterial pressure and flow are abnormally increased at birth, as in coarctation with patent ductus and ventricular septal defect, an increase in arterial diameter and muscularity is apparent within the first week of life.

Aorta, Thoracic↗
PubMed1983

Regional blood flow with first circulation time-indicator curves: a simplified, physiologic method of interpretation.

Dynamic computed tomography, digital subtraction angiography, and radionuclide angiography can all be used to evaluate regional blood flow noninvasively. In each case an indicator is injected intravenously and time-indicator curves are generated from regions of interest during the first circulation. Although regional blood flow cannot be determined uniquely from first circulation time-indicator curves, relative transit time to and through the regions of interest and relative regional blood volume in the regions of interest can be measured and related to relative regional blood flow using a modified Stewart-Hamilton equation. However, for precise mathematical calculation, extrapolation of the first circulation data beyond the point of recirculation is required. This extrapolation is inconvenient and difficult to perform accurately and reproducibly. Indices of transit time and regional volume that do not require extrapolation were evaluated in an experimental model. The correlation coefficients between the indices of transit time and volume and the more mathematically precise measurements were 0.99 and 0.95, respectively (p less than 0.01). It is suggested that these indices, which can also be evaluated visually, are useful in interpreting first circulation time-indicator curves in a physiologic manner.

Blood Circulation Time↗
PubMed1990

Na restriction blunts expansion of plasma volume and ameliorates hyperdynamic circulation in portal hypertension.

Expansion of plasma volume may be necessary for the development of the hyperdynamic circulation in portal hypertension. In experiment 1, sham portal vein-constricted (sham PVL) rats were divided into normal diet (NL diet sham) and low-sodium diet (low-Na sham) groups. Data obtained from the NL diet sham group was used as control data in studying portal hypertensive rats, which were also divided into normal diet (NL diet PVL) and sodium-restricted (low-Na PVL) groups on the day of portal vein constriction. There were no hemodynamic differences at 3 wk between sham PVL rats on the two diets. In contrast, sodium restriction in PVL rats resulted in a significant amelioration of the hyperdynamic circulation. In experiment 2, PVL rats were fed a normal diet for 10 days, followed by allocation to NL diet PVL and low-Na PVL groups. The hemodynamic effects of sodium restriction in these animals (studied at 22 and 28 days after PVL) were similar to those observed in experiment 1. A time course for amelioration of the hyperdynamic circulation in PVL rats by sodium restriction is described. Sodium restriction prevents the expansion of the plasma volume in PVL rats. Interference with plasma volume expansion blunts the development of (and can ameliorate) the hyperdynamic syndrome. Plasma volume expansion seems necessary for the development of the hyperdynamic circulation in portal hypertension.

Animals↗
PubMed1996

Dorsal aortic impedance in stage 24 chick embryo following acute changes in circulating blood volume.

The effects of acute changes in circulating blood volume on embryonic vascular hemodynamics were evaluated with the use of input impedance. We simultaneously measured dorsal aortic pressure with a servo-null system and flow velocity with a 20-MHz pulsed Doppler system in n = 90 stage 24 chick embryos. We withdrew or infused 1,3, or 5 microliters of blood via a second-order vitelline vein (n = 10 per group). In addition, we withdrew and then infused or infused and then withdrew 3 microliters (n = 5 per group). Characteristic impedance, peripheral resistance, arterial compliance and elastance, and hydraulic power as well as basic hemodynamic parameters were evaluated on the basis of the three-element windkessel model. In response to withdrawal, mean and pulse pressure, mean flow, arterial compliance, and hydraulic power decreased, whereas peripheral resistance and arterial elastance increased in a dose-dependent manner. Results in response to infusion were converse in effect. Characteristic impedance was unchanged by volume alternations. Oscillatory fraction of hydraulic power was higher than mature circulation and remained relatively constant during interventions, which indicates well-regulated energy efficiency for vascular growth in the embryonic circulation. A hysteresis relevant to altered peripheral resistance was present after multiple interventions. Embryonic vasculature is sensitive to circulating blood volume and preserve blood pressure at the expense of blood flow. In the absence of autonomic innervation, embryonic vascular tone may be regulated by mechanical properties of the vessel (the law of Laplace) and/or vasoactive substances.

Animals↗
PubMed1998

Carl J. Wiggers and the pulmonary circulation: a young man in search of excellence.

Oddly, Carl Wiggers (1883-1962), who is remembered for his work on the systemic circulation, may be considered the "American father of the pulmonary circulation." In nearly-20 papers published in the American Journal of Physiology between 1909 and 1925, he reported the first reliable pressure contours in the pulmonary artery, inquired into the relationship between respiration and pulmonary arterial pressure, examined right atrial and right ventricular function, and demonstrated how right and left heart dynamics relate to heart sounds. He also stimulated direct visualization of the lung microcirculation. Method and concept are inextricably linked in the progress of science. His contributions to the pulmonary circulation were based on his high-fidelity pressure and sound recording instruments, which he ultimately applied in the left heart. Wiggers' search for excellence in method brought him well-deserved fame in the systemic circulation, but the search began in the lung.

History, 20th Century↗
PubMed1985

Mathematical model of fetal circulation and oxygen delivery.

To better understand the fetal circulation and its regulation we constructed a dynamic model of fetal circulation as a transport system. The fetal vascular system is divided into 16 compartments which incorporate the peculiarities of the fetal circulation that produce a difference in oxygen concentration in blood supplying the upper and lower body. Recently published data is used to provide a firm experimental base for the model. The model is used to examine how the results on parts of the fetal cardiovascular system and fetal oxygen consumption are compatible and form a coherent description. We also studied the effects of disturbances from the normal steady state produced by changes in patterns of and resistances to blood flow. A maternal placental blood flow of less than 200 ml X min-1 X kg fetal wt-1 produces a steady-state value of oxygen tension in the fetal ascending aorta of less than 17 mmHg, which is incompatible with normal oxygen delivery. A minimal value of umbilical flow providing an adequate oxygen supply to the fetal body is 87 ml X min-1 X kg fetal wt-1. Due to the geometry of the fetal circulation, the highest normal oxygen tension in the fetal ascending aorta is approximately 25 mmHg, only 8 mmHg above the lowest normal tension of 17 mmHg. Dynamic studies using the model demonstrate differences in response of fetal arterial oxygen tension to temporal cord occlusion and temporal decrease in maternal placental flow.

Blood Circulation↗
PubMed1996

Sensitivity of the renal medullary circulation to plasma vasopressin.

Studies were carried out to determine the effects of physiological changes of plasma arginine vasopressin (AVP) on blood flow distribution in the renal cortex and medulla. Acute decerebration was performed so that studies could be carried out within the low physiological range of circulating AVP. Changes of renal cortical and medullary microcirculatory blood flow were measured with implanted optical fibers and laser-Doppler flowmetry, and total renal blood flow was measured with transit-time ultrasonography. During intravenous infusion of increasing doses of AVP, when plasma AVP was increased in steps from 2.9 to 11.2 pg/ml by intravenous infusion, mean arterial pressure (98 +/- 3 mmHg), total renal blood flow (8.2 +/- 0.6 ml. min-1.g kidney-1), and blood flow in the microcirculation of the cortex (2.11 +/- 0.28 V) remained unchanged, whereas that in the renal medulla decreased progressively. Medullary flow was significantly reduced when circulating levels of AVP increased from a control level of 2.8 to 5.0 pg/ml. The reductions of medullary flow were accompanied by parallel increases of urine osmolality. These data indicate that the vessels supplying the renal medullary circulation are sensitive within the range of plasma AVP concentrations observed with moderate water restriction. The medullary circulation exhibits a sensitivity AVP that parallels that found in the medullary collecting ducts.

Animals↗
PubMed2001

Effects of catecholamines on the pulmonary circulation in the ovine fetus.

High levels of circulating catecholamines are found in the fetus, and fetal stress and birth induce a marked surge in catecholamine secretion. Little is known about the role of catecholamines on the fetal pulmonary circulation. To determine the effects of catecholamines on the pulmonary vascular tone, we tested the hemodynamic response to norepinephrine and dopamine infusion in chronically prepared late-gestation fetal lambs. We found that norepinephrine infusion (0.5 microg. kg(-1). min(-1)) increased pulmonary artery pressure (PAP) by 10 +/- 1% (P < 0.01), left pulmonary artery blood flow by 73 +/- 14% (P < 0.01), and decreased pulmonary vascular resistance (PVR) by 33 +/- 6% (P < 0.01). The pulmonary vasodilator effect of norepinephrine was abolished after nitric oxide synthase inhibition. Dopamine infusion at 5 microg. kg(-1). min(-1) did not significantly change PVR. Conversely, dopamine infusion at 10 microg. kg(-1). min(-1) increased PAP (P < 0.01) and progressively increased PVR by 30 +/- 14% (P < 0.01). These results indicate that catecholamines may modulate basal pulmonary vascular tone in the ovine fetus. We speculate that catecholamines may play a significant role in the maintenance of the fetal pulmonary circulation and in mediating changes in the transitional pulmonary circulation.

Adrenergic alpha-Agonists↗
PubMed1982

Fate of [125I]insulin removed from the peritubular circulation of isolated perfused rat kidney.

Although there is considerable evidence that insulin is removed from the peritubular circulation of the mammalian kidney, it is unclear whether binding to insulin-specific receptors is involved in this process, whether after peritubular removal the hormone is degraded to small fragments with release into the circulation, or whether it merely undergoes a minor modification with loss of immunoreactivity. We examined the metabolism of [125I]insulin removed from the peritubular circulation of the nonfiltering isolated perfused rat kidney and compared it to that of [125I]insulin metabolized by filtering isolated kidneys and kidney homogenates. The results indicate that after peritubular removal, a small amount of insulin is degraded to form low-molecular-weight products similar to those seen with filtering kidneys and kidney homogenates. However, most of the insulin removed from the peritubular circulation is processed either to nonimmunoreactive products of molecular weight similar to that of insulin or, to a lesser extent, to products of larger molecular weight. Both these products are also formed by filtering kidneys. In the filtering kidney, the products having molecular weight similar to that of insulin probably originate from the peritubular process, because it is unlikely that material of this size could be derived from the filtration-absorption pathway. Of particular note was the finding that [125I]insulin trapped in the peritubular compartment of nonfiltering kidneys was displaced severalfold more effectively by unlabeled insulin than by several peptide hormones (P less than 0.01); the latter were no more effective than vehicle alone. The findings suggest the presence of peritubular insulin-specific receptors.

Animals↗
PubMed1985

Interaction between cold and altitude exposure on pulmonary circulation of cattle.

Hereford calves were exposed in a temperature-controlled hypobaric chamber to environmental temperatures of -2 to 1 degree C (cold) at altitudes of 1,524 m (resident altitude) and 3,048 m 1) to characterize the effects of cold exposure on the pulmonary circulation; 2) to examine the role of cold-induced hypoventilation on the pulmonary circulation; and 3) to examine the interaction between cold and hypoxia on the pulmonary circulation. Cold exposure produced a significant increase in pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppaw), and pulmonary vascular resistance (PVR) at both 1,524 and 3,048 m without affecting cardiac output. Concomitantly, cold exposure caused reductions in minute ventilation, respiratory rate, end-tidal O2 tension (PETO2), and arterial O2 tension (PaO2). Tidal volume, end-tidal CO2 tension, and arterial CO2 tension increased. Neither arterial pH nor O2 consumption changed during cold exposure. These results indicated that both pulmonary arterial and venous vasoconstriction were responsible for the pulmonary hypertension associated with cold exposure. Acute exposure to 3,048 m during cold exposure produced increases in Ppa and PVR that were similar to those elicited by cold exposure at 1,524. It was concluded that altitude exposure neither attenuated nor potentiated the effect of cold exposure on the pulmonary circulation; rather, altitude and cold exposure interacted additively. O2 administered during cold exposure to restore PETO2 and PaO2 to control values partially restored Ppa and PVR to control values. This suggested that a portion of the pulmonary hypertension associated with cold exposure was due to hypoxic pulmonary vasoconstriction elicited by the cold-induced alveolar hypoventilation.

Altitude↗
PubMed1986

Hyperventilation, alkalosis, prostaglandins, and pulmonary circulation of the newborn.

This study was designed to determine whether the effects of hyperventilation on the pulmonary circulation of the newborn lamb were 1) due to mechanical factors or to respiratory alkalosis; and 2) mediated by prostaglandins. Six control lambs were studied during normal ventilation and during hyperventilation with, and without, decreased carbon dioxide (CO2). Five lambs were given indomethacin and studied similarly. In control lambs, hyperventilation with decreased CO2 decreased pulmonary arterial pressure from 26 +/- 2.2 to 18 +/- 1.0 (SE) Torr (P less than or equal to 0.005) and pulmonary vascular resistance from 0.099 +/- 0.035 to 0.070 +/- 0.011 Torr X kg-1 X min-1 (P less than or equal to 0.015). Hyperventilation with normal CO2 did not affect the pulmonary circulation. Hyperventilation with decreased CO2 increased pulmonary arterial concentrations of 6-ketoprostaglandin F1 alpha, a major metabolite of prostacyclin, in control lambs but not in the indomethacin-treated lambs. However, it affected the pulmonary circulation of the control- and indomethacin-treated lambs similarly. In conclusion, hyperventilation affected the pulmonary circulation by respiratory alkalosis not by mechanical factors and prostaglandins did not mediate its effects.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ.

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

Animals↗
PubMedDate not supplied

Measurement of cerebral circulation time by contrast-enhanced Doppler sonography.

We present a new, non-invasive ultrasound method for the measurement of cerebral circulation time. After injection of a galactose-based echo-contrast agent (Levovist) into an antecubital vein, cerebral circulation time is measured as the interval between the beginning of a stable signal enhancement of at least 5 dB in the internal carotid artery and in the ipsilateral internal jugular vein. Both vessels are insonated simultaneously at the mandibular angle using a single 2-MHz range-gated transducer. For this study, 25 healthy volunteers ranging in age from 23 to 55 years (30.1 +/- 7.5 years; mean +/- SD) were examined. Cerebral circulation time was 5.6 +/- 1.7 s without significant side-to-side or sex-related differences. Measurement of circulation times offers a new possibility for the employment of echo-contrast agents in functional ultrasound.

Adult↗
PubMed2003

Molecular detection of circulating cancer cells. Role in diagnosis, prognosis and follow-up of colon cancer patients.

BACKGROUND: The circulating tumor cells of solid tumors, especially in colorectal cancer has been of great interest in medical research in the last and new century. METHODS: A literature review of recent data for the preparation of a proposal for clinical applications. RESULTS: Starting with the detection of circulating cancer cells in histological sections, lymph nodes, bone marrow and peripheral blood have recently become the primary samples for these investigations. Following microscopic morphology, new methods were and are being developed continuously including rare cell enrichment and detection techniques like fluorescence microscopy, flow cytometry, RT-PCR and methylated DNA PCR. The sensitivity of these assays reaches down to the concentration of 1 tumor cell/ml blood. A lot of different epithelial markers were targeted with these techniques e.g. cytokeratins, EGFR, CEA, and EMA. Clinically, circulating tumor cells were found as independent prognostic factors in lymph nodes and bone marrow. In blood, their presence appears to be an early marker for recurrence and relapse. The change in their quantitative number is supposed to reflect the chemotherapeutic sensitivity and metastatic growth activity of the tumor. CONCLUSIONS: The detection of circulating tumor cells in bone marrow and lymph nodes is of clinical significance. Their presence in peripheral blood and therapeutic applications need further clarification.

Biomarkers, Tumor↗
PubMed2006

Magnetic resonance evaluation of the cerebral circulation in obstructive arterial disease.

BACKGROUND: The aim of the current overview is to highlight the possibilities of magnetic resonance imaging (MRI) in the assessment of patients with obstructive arterial disease. The anatomic and hemodynamic aspects of the extra- and intracranial cerebral circulation were analyzed and show the importance of combining both aspects in studying cerebral hemodynamic changes. RESULTS: Three levels of cerebral circulation are distinguished: blood flow to the brain (level 1); the distribution of blood flow in the brain (level 2), and finally perfusion of the brain (level 3). To investigate the anatomy of the arteries in the neck and the circle of Willis, contrast-enhanced, time-of-flight and phase contrast MR angiography (MRA) are available. To evaluate the hemodynamics at the 1st and 2nd level of the cerebral circulation two-dimensional phase contrast (volume flow and flow direction) MRA can be used. In addition, the distribution of blood via the circle of Willis can be visualized with dynamic MRA. At the 3rd level, measurements of regional brain perfusion can be obtained by injecting gadolinium, dynamic susceptibility contrast MRI, or noninvasively with arterial spin labeling (ASL) MRI. In addition, selective ASL MRI is able to evaluate the perfused territories of individual brain-feeding arteries. CONCLUSION: The currently available MR techniques allow evaluation of the cerebral circulation from the aortic arch upwards towards the microvasculature and brain tissue perfusion in a comprehensive 20-min protocol. The combined use of the described MR methods in patients with steno-occlusive disease will further clarify the pathophysiological relations between the vasculature, perfusion and brain function.

Arterial Occlusive Diseases↗
PubMed1987

Interaction of dopamine, (+/-)-dobutamine and the (-)-enantiomer of dobutamine with alpha- and beta-adrenoceptors in the pulmonary circulation of the dog.

The effects of dopamine, (+/-)-dobutamine (racemic mixture) and (-)-dobutamine on alpha-adrenoceptor-mediated vasoconstriction were evaluated in the pulmonary circulation of the anesthetized dog. The drugs were studied in the absence and presence of propranolol (1 mg/kg, i.v.) in order to assess beta-adrenoceptor-mediated effects in the pulmonary circulation. Intra-arterial administration of dopamine, (+/-)-dobutamine and (-)-dobutamine elicited dose-dependent increases in pulmonary perfusion pressure, reflecting increases in pulmonary vascular resistance. In control animals, dopamine elicited the largest increases in pulmonary perfusion pressure (45% above resting pulmonary pressure) followed by (-)-dobutamine (30% increase) and (+/-)-dobutamine (15% increase). The pressor effects of dopamine in the pulmonary circulation were mediated by both postjunctional vascular alpha 1- and alpha 2-adrenoceptors, since prazosin, (100 micrograms/kg, i.v.), a selective alpha 1-adrenoceptor antagonist, and rauwolscine (100 micrograms/kg, i.v.), a selective alpha 2-adrenoceptor antagonist, both inhibited the vasopressor response elicited by dopamine to roughly equivalent degrees. Pulmonary vasoconstriction produced by (+/-)-dobutamine and (-)-dobutamine was mediated primarily by postsynaptic vascular alpha 1-adrenoceptors, although alpha 2-adrenoceptor-mediated vasoconstriction was observed. In propranolol-pretreated animals, the increase in pulmonary perfusion pressure elicited by dopamine and (-)-dobutamine was qualitatively and quantitatively similar to that observed in control animals, suggesting that these agents have little activity on vascular beta 2-adrenoceptors in the pulmonary circulation. In marked contrast, the maximum pulmonary vasopressor response obtained with (+/-)-dobutamine were greater in propranolol-pretreated animals, indicating that (+/-)-dobutamine also has the capacity to stimulate pulmonary vascular beta 2-adrenoceptors which mediate pulmonary vasodilation that, in part, mask alpha-adrenoceptor-mediated pulmonary vasoconstriction. Since the (-)-enantiomer of dobutamine has little or no beta 2-adrenoceptor agonist activity, the beta 2-adrenoceptor-mediated effect of (+/-)-dobutamine must result from the (+)-enantiomer as has been previously proposed. The results of the present study indicate that dopamine has a greater propensity for increasing pulmonary vascular resistance, and therefore pulmonary arterial blood pressure, relative to (+/-)-dobutamine. This results, at least in part, from the relatively weaker activity of dopamine in stimulating pulmonary vascular beta 2-adrenoceptors which mediate vasodilation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1998

Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases during the second half of pregnancy: a randomized study.

BACKGROUND: The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation. METHODS AND RESULTS: Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were randomized to receive either 60% humidified oxygen or medical compressed air (room air) by a face mask. Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air. Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Qp) were calculated. Foramen ovale volume blood flow (left ventricular cardiac output-Qp) was estimated. Pulsatility index (PI) values of DA, RPA, LPA, and DPA were calculated. Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks, whereas between 31 and 36 weeks, the PI values of RPA, LPA, and DPA decreased (P<.0001) and the PI of DA increased (P<.0001). In addition, Qp increased (P<.001), and DA volume blood flow (P<.01) and foramen ovale volume blood flow (P<.03) decreased. Left and right ventricular cardiac outputs were unchanged. All changes returned to baseline after maternal hyperoxygenation was discontinued. CONCLUSIONS: Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation.

Blood Flow Velocity↗
PubMed1989

Transmission of hypertension in rats by cross circulation.

Cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. Blood was pumped through two anastomoses between the carotid arteries and external jugular veins in both directions with equal flow rate. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9 +/- 12.2 mm Hg (p less than 0.01). Administration of digoxin antibody in a dose binding 0.25 mg digoxin to the spontaneously hypertensive rats before cross circulation prevented the transmission of hypertension to the normotensive rat, whereas chemical sympathectomy with 6-hydroxydopamine and intravenous injection of inactive Fab fragments had no inhibitory effect. It is concluded that, in this strain of spontaneously hypertensive rats, a circulating hypertensive factor exists. The factor binds to digoxin antibody and is not produced in sympathetic nervous tissue.

Animals↗