Rebound hemodynamic events after the abrupt withdrawal of nitroprusside in patients with severe chronic heart failure

We studied the hemodynamic events that followed abrupt withdrawal of nitroprusside in 20 patients with severe chronic heart failure. With nitroprusside, cardiac index increased from 1.96 to 2.87 liters per minute per square meter of body-surface area, but it decreased to 1.66 (P less than 0.001) after withdrawal of nitroprusside. Left ventricular filling pressure and systemic vascular resistance decreased from 23.9 to 15.3 mm Hg and from 1642 to 921 dyn.sec.cm-5, respectively, with nitroprusside, but increased to 30.4 mm Hg and 2109 dyn.sec.cm-5 (both P less than 0.001) upon its discontinuation. These rebound changes were maximal 10 to 30 minutes after nitroprusside withdrawal and returned to control levels one to three hours later. Although in 17 of 20 patients, these rebound changes caused no or minimal exacerbation of symptoms, pulmonary edema, which resolved in three patients. Activation of reflex vasoconstrictive forces during vasodilator therapy may explain these effects of withdrawal.     

5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver

Mice lacking 5-HT 2C receptors (5-HT(2C)Rs) displayed hepatic insulin resistance, a phenotype normalized by re-expression of 5-HT(2C)Rs only in pro-opiomelanocortin (POMC) neurons. 5-HT(2C)R deficiency also abolished the anti-diabetic effects of meta-chlorophenylpiperazine (a 5-HT(2C)R agonist); these effects were restored when 5-HT(2C)Rs were re-expressed in POMC neurons. Our findings indicate that 5-HT(2C)Rs expressed by POMC neurons are physiologically relevant regulators of insulin sensitivity and glucose homeostasis in the liver.     

Acute reversal by saralasin of multiple intrarenal effects of angiotensin II.

Glomerular hemodynamics were measured by micropuncture technique in the plasma volume-expanded Munich-Wistar rat in 1) a control group, 2) during a pressor infusion of angiotensin II (AII), and 3) during simultaneous infusions of AII and saralasin, which returned arterial pressure to normal. Respective values obtained in the three groups studied were: nephron filtration rate: 60 +/- 2 vs. 40 +/- 2 vs. 42 +/- 2 nl.min-1.g kidney wt-1; nepphron plasma flow: 263 +/- 13 vs. 106 +/- 5 vs. 165 +/- 13 nl. min-1.g kidney wt-1; LpA, the glomerular permeability coefficient: 0.090 +/- 0.009 vs. 0.033 +/- 0.005 vs. 0.103 +/- 0.020 nl.s-1.g kidney wt-1. mmHg-1; afferent arteriolar resistance: 10.2 +/- 0.7 vs. 25.1 +/- 1.3 vs. 19.7 +/- 3.3 10(9) dyn.s.cm-5; efferent arteriolar resistance: 7.8 +/- 0.5 vs. 22.0 +/- 0.9 vs. 10.8 +/- 1.7 10(9) dyn.s.cm-5. Saralasin acutely reversed the effect of AII on both efferent resistance and LpA, suggesting that AII does not decrease LpA by inducing a fixed anatomic change. For unclear reasons, saralasin did not reverse the increase in afferent resistance associated with infusion of AII. Saralasin infusion in high AII states may acutely affect glomerular hemodynamics by decreasing efferent resistance and increasing the glomerular permeability coefficient.     

Twenty-four-hour pattern of circulation by radiotelemetry in the unrestrained dog.

Eight dogs with indwelling transducers for continuous radiotelemetry of the hemodynamic function were acclimatized in an unisolated room under 12:12 LD photoperiods, in phase with the solar day cycle, and constant temperature (20 +/- 1 degrees C). Light was turned on at 0600 and off at 1800. Mean aortic blood flow (ABF), mean aortic blood pressure (ABP), heart rate (HR), respiratory rate (RR), and cardiac work (CW) were maximal at about 1800 and minimal at time 0600. Total peripheral resistance (TPR) was highest and stroke volume (SV) lowest at about 1200. The 24-h mean was for HR 77 beats/min, SV 28 ml/beat, RR 11 breaths/min, ABF 177 ml/min per kg body wt, ABP 102 Torr, TPR 3,960 dyn . s . cm-5, and CW 218 Torr . 1/min. The range of amplitude fluctuations for daytime means was about 6% for ABP and SV and 11-17% for all others. It is suggested that the homeostatic balance and timing of circulation is circadian time dependent.     

The prognostic value of haemodynamic tests in chronic bronchitis (author's transl)

The prognostic value of several functional respiratory and haemodynamic variables was studied in a group of 212 patients with chronic bronchitis, who were examined in steady state, without cardiac or respiratory failure, at rest and when possible during moderate exercise (195 patients). Follow-up interval ranged from 5 to 12 years. Results were processed using two methods: estimation of actuarial survival rate and discriminant analysis. Survival rate curves for the patients showed a reduction relative to the general population of the same ages: 74% within five years compared to 91% in the general population, 56% within nine years compared to 82%. Survival rate was significantly lower in patients with PPA above 30 mmHg, or driving pressure (PPA--PW) above 15 mmHg, or pulmonary vascular resistance higher than 210 dyn . s . cm-5, or when PPA increased more than 10 mmHg during exercise. Discriminant analysis underlined the predictive value of three haemodynamic variables: PPA change from rest to exercise, pressure developed by the right heart (PPA--PRVED) and stroke volume: together, they predict the death of 3 over 4 patients with the criteria chosen.     

Tonic release of transmitter at the neuromuscular junction of the crab.

1. Synaptic transmission was studied at the neuromuscular junction of the crab Ocypoda cursor, using conventional electrophysiological technique. 2. It was found that fibres of the extensor muscle and those composing the internal layer of the closer muscle have only post-synaptic inhibition (S fibres) while the fibres at the external layer of the closer muscle have in addition presynaptic inhibition (R fibres). 3. In S fibres, addition of GABA reduces input membrane resistance (Rm) and e.p.s.p. amplitude approximately to the same degree. The effect shows desensitization. In R type fibres, GABA reduces the e.p.s.p. much more than expected from changes in Rm. The post-synaptic effect of GABA on Rm shows desensitization, while the presynaptic effect does not show desensitization. 4. In about 50 percent of the cases, after desensitization occurred, Rm increased by about 10-30 percent above the control. Similar increase in Rm occurred after application of picrotoxin. These results suggest that initially the membrane resistance was lower due to tonic release of inhibitory transmitter. 5. The Q10 of Rm was found to vary between 2 and 3. In Ca2+ free media, Cl- free media, or in picrotoxin the Q10 is about 1-3. 6. In R fibres, addition of picrotoxin increased the amplitude of the e.p.s.p. by 30-60 percent above the expected increase due to changes in Rm. 7. In S fibres the mean slope of log e.p.s.p. vs. log [Ca2+] was found to be 1-63, while in R fibres the slope was 0-93. These results suggest the presence of tonic release of the inhibitory transmitter which acts both post-synaptically and presynaptically.     

Effects of Aging on Antioxidant Response and Phagocytosis in Senescent Erythrocytes

Red blood cell (RBC) aging is a complex process affected by immunological and biochemical parameters. In this work we studied the antioxidant response in RBC of different ages. We also investigated their interaction with peripheral blood monocytes. Anticoagulated blood samples from 19 O RhD+ volunteers' donors were processed. Young (Y) RBC and Senescent (Se) RBC were obtained by self-formed gradients of Percoll. The fractionation of the erythrocytes suspensions was demonstrated by statistically significant density-related changes in hematological determinations. Activities of glucose-6-phosphate dehydrogenase (G6PD), of soluble NADH-cytochrome b5 reductase (b5Rs) and membrane-bound b5R (b5Rm) were determined spectrophotometrically. The interaction between monocytes and different RBC suspensions was evaluated by the erythrophagocytosis assay. The G6PD and b5Rm activities in SeRBC were significantly lower than that observed in YRBC. No differences were found in the b5Rs of both groups. We observed an increased rate of erythrophagocytosis the SeRBC compared to YRBC. The decline in the activities of G6PD and b5Rm would indicate a decrease in the antioxidant response associated to RBC aging. These findings would signify that the oxidative changes of membrane occurring during the life span of the RBC might be relevant in the process of removal of SeRBC from the circulation.     

Respiratory input and transfer impedances in children 9-13 years old

Reference values for respiratory impedances in children are scarce and limited to the situation where pressure is varied at the mouth. Total respiratory impedance was therefore measured from 4 to 30 Hz in 69 healthy children (9-13 yr) with both a pressure input at the mouth (input impedance, Zin) and a pressure input at the chest (transfer impedance, Ztr). Zin was characterized by the average resistance (R), the low-frequency limit of resistance (R0), the slope of the resistance-frequency curve (S), respiratory elastance (E) and respiratory inertance (I). Similar coefficients (R0', S', E', I'), some of which however have slightly different physiological meanings, were derived from Ztr. R, R0 and R0' were found to be significantly correlated to body height (p less than 0.001) and, independently, to age (p less than 0.05): R (kPa X l-1 X s) = 1.76-5.29 10(-3) height (cm) -4.13 10(-2) age (yr). Elastances were better correlated to height than to age: E (kPa X l-1) = 20.95-0.101 height (cm) and inertances better correlated to age than to height: I (Pa X l-1 X s2) = 4.39-0.128 age (yr). S and S' were not correlated to biometric variables. No difference was found between children living in polluted (n = 36) and nonpolluted (n = 33) areas, except for S which was significantly lower in the first group (p less than 0.01).     

Mental stress increases right heart afterload in severe pulmonary hypertension.

Little is known about mental stress effects on the pulmonary circulation in health and disease. The current study was conducted to investigate whether pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) would further increase during standardized mental stress testing in patients with severe pulmonary hypertension. The study was a prospective analysis of seven patients (average age: 40 years, range from 21 to 56 years) with severe pulmonary hypertension (primary: n = 4, secondary forms: n = 3; resting mean pulmonary artery pressure ranged between 48 and 65 mmHg). Right heart catheterization for the determination of PAP, pulmonary capillary wedge pressure (PCW) and cardiac output (CO) was clinically indicated (diagnostic workup, acute drug testing). Patients accomplished a standardized 10 min mental stress test (computer based, adaptive complex reaction-time task). Pulmonary haemodynamics during stress were compared to resting baseline. During mental stress mean PAP (+/- SEM) increased by 9.4 +/- 2.1 mmHg (P < 0.005). Pulmonary vascular resistance increased by 149 +/- 25 dyne s cm-5 (P < 0.001). Stroke volume decreased by 6.6 +/- 2.2 ml (P < 0.03). The data show that moderate mental stress increases right heart afterload in patients with severe pulmonary hypertension owing to elevation of PVR.     

Pediatric impedance cardiography: temporal stability and intertask consistency

The pathogenic processes responsible for cardiovascular disease have their origins in childhood. Although children's measures of heart rate and blood pressure have been found to be reliable, the reliability of impedance cardiography derived measures have not been evaluated. Thirty-three children, ages 8-11 participated in two sessions. Stressors included serial subtraction, isometric handgrip, and mirror-image tracing. Results indicated the impedance measures showed moderately high temporal stability (average scores r(avg) = .74; difference scores r(avg) = .53) and intertask consistency (average scores r(avg)= .78; difference scores r(avg)= .53). Blood pressure demonstrated the lowest reliability; Heather index, preejection period, and stroke volume demonstrated the highest. These findings suggest children's cardiovascular reactivity to laboratory stressors can be reliably and consistently assessed using impedance cardiography.     

Role of vascular bed compliance in vasomotor control in human skeletal muscle

The current view of neurogenic vasomotor control in skeletal muscle is based largely on changes in vascular bed resistance. The purpose of this study was to determine to what extent vascular bed compliance may also play a role in this regulation. For this purpose, pressure waveforms (Millar and Finometer) and flow waveforms (Doppler ultrasound) were measured simultaneously in the brachial artery of seven healthy individuals during physiological manoeuvres which were expected to produce non-neurogenic changes in resistance (wrist-cuff occlusion; n = 5) or compliance (arm elevation; n = 6) of the forearm vascular bed. Vascular resistance (R) was calculated from the average flow and pressure values. A lumped Windkessel model was used to obtain vascular bed compliance (C) from these concurrently measured waveforms. Compared with baseline (3.81 +/- 1.59 ml min(-1) mmHg(-1)), wrist occlusion increased R (65 +/- 75%; P < 0.05) with minimal change in C (-15 +/- 16%; n.s.). Compared with the arm in neutral position (0.0075 +/- 0.003 ml mmHg(-1)), elevation of the arm above heart level produced a 86 +/- 41% increase in C (P < 0.05) with little change in R (-5 +/- 11%). In addition, neurogenic changes were assessed during lower body negative pressure (LBNP) and a cold pressor test (CPT; n = 7). Lower body negative pressure induced a 29 +/- 24% increase in R and a 26 +/- 12% decrease in C (both P < 0.05). The CPT induced no consistent change in R but a 22 +/- 7% reduction in C (P < 0.05). It was concluded that vascular bed compliance is an independent variable which should be considered along with vascular bed resistance in the mechanics of vasomotor regulation in skeletal muscle.     

Calpain inhibition preserves talin and attenuates right heart failure in acute pulmonary hypertension

Right heart failure from right ventricular (RV) pressure overload is a major cause of morbidity and mortality, but its mechanism is incompletely understood. We tested the hypothesis that right heart failure during 4 hours of RV pressure overload is associated with alterations of the focal adhesion protein talin, and that the inhibition of calpain attenuates RV dysfunction and preserves RV talin. Anesthetized open-chest pigs treated with the calpain inhibitor MDL-28170 (n = 20) or inactive vehicle (n = 23) underwent 4 hours of RV pressure overload by pulmonary artery constriction (initial RV systolic pressure, 64 ± 1 and 66 ± 1 mm Hg in MDL-28170 and vehicle-treated pigs, respectively). Progressive RV contractile dysfunction was attenuated by MDL-28170: after 4 hours of RV pressure overload, RV systolic pressure was 44 ± 4 mm Hg versus 49 ± 6 mm Hg (P = 0.011), and RV stroke work was 72 ± 5% of baseline versus 90 ± 5% of baseline, (P = 0.027), in vehicle-treated versus MDL-28170-treated pigs, respectively. MDL-28170 reduced the incidence of hemodynamic instability (death or systolic blood pressure of < 85 mm Hg) by 46% (P = 0.013). RV pressure overload disrupted talin organization. MDL-28170 preserved talin abundance in the RV free wall (P = 0.039), and talin abundance correlated with the maintenance of RV free wall stroke work (r = 0.58, P = 0.0039). α-actinin and vinculin showed similar changes according to immunohistology. Right heart failure from acute RV pressure overload is associated with reduced talin abundance and disrupted talin organization. Calpain inhibition preserves the abundance and organization of talin and RV function. Calpain inhibition may offer clinical utility in treating acute cor pulmonale.     

Pulmonary vascular resistance rises with lung volume on exercise in obstructed airflow disease

There has been experimental evidence that lung distension produces an increase in pulmonary vascular resistance (PVR). To study this effect in patients, we measured functional residual capacity (FRC) by helium dilution at rest and during low-load supine exercise in 30 patients with chronic obstructive pulmonary disease. Pulmonary haemodynamics were studied in these patients under the same conditions. FRC increased from rest (4.32 +/- 0.21 l) to exercise (4.71 +/- 0.20, P less than 0.001) but the change was smaller in the patients with the highest FRC at rest: there was a significant negative correlation between FRC change and FRC at rest (r = -0.38, P less than 0.01). There were seven patients with a small FRC change (less than 0.2 l) with exercise and 10 patients with a marked increase (greater than 0.5 l). Exercise was of the same load on average. FRC at rest was 5.1 l in the first group and 4 l in the second (P less than 0.05). Blood gases were almost identical at rest, and almost unchanged during exercise. PVR decreased from rest to exercise by 33 dyn.s.cm-5 in the first group and increased by 24 in the second (P less than 0.01). There was a significant correlation (P less than 0.05) between PVR and FRC changes from rest to exercise. These results suggest that lung distension may play a role in the PVR increase seen in some COPD patients with exercise.     

Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia

To determine whether prostaglandins are involved in circulatory homeostasis in congestive heart failure, we measured plasma levels of the metabolites of vasodilator prostaglandins I2 and E2 in 15 patients with severe chronic heart failure. Mean circulating levels of both metabolites were 3 to 10 times higher than those in normal subjects. Plasma levels of both metabolites correlated directly with plasma renin activity and plasma angiotensin II concentrations (r = 0.64 and 0.84, respectively). Individual serum sodium concentrations were inversely correlated with levels of prostaglandin E2 metabolites (r = -0.92, P less than 0.001) and plasma renin activity (r = -0.69, P less than 0.02). Of 23 patients with severe heart failure challenged with indomethacin (an inhibitor of prostaglandin synthesis), the 9 with hyponatremia had significant decreases in the cardiac index (1.99 +/- 0.12 to 1.72 +/- 0.13 liters per minute per square meter of body-surface area, P less than 0.001) and significant increases in the pulmonary capillary wedge pressure (17.4 +/- 2.0 to 24.0 +/- 1.9 mm Hg, P less than 0.001) and systemic vascular resistance (1882 +/- 239 to 2488 +/- 315 dyn x sec x cm-5, P less than 0.001), whereas the 14 patients with a normal serum sodium concentration had no significant hemodynamic changes. We conclude that both vasoconstrictor (renin-angiotensin) and vasodilator (prostaglandin) mechanisms are operative in patients with heart failure complicated by hyponatremia and that these mechanisms interact to modulate circulatory homeostasis.     

Elevated arterial blood pressure in cardiac tamponade.

BACKGROUND. In cardiac tamponade cardiac output falls, but peripheral vascular resistance increases, so that systemic blood pressure may be maintained at normal or near-normal levels. We recently observed a patient with cardiac tamponade whose blood pressure was markedly elevated. METHODS. To determine the frequency of elevated blood pressure in patients with cardiac tamponade and their hemodynamic characteristics, we studied 18 consecutive patients with cardiac tamponade from a variety of causes using right heart catheterization. RESULTS. Six of the 18 patients had systolic arterial blood pressures ranging from 150 to 210 mm Hg (mean [+/- SD], 176 +/- 26) and diastolic pressures ranging from 100 to 130 mm Hg (mean, 113 +/- 14). All six had previously been hypertensive. After pericardiocentesis there was a significant decrease in blood pressure (to 139 +/- 13 mm Hg systolic, P less than 0.05; and 83 +/- 6 mm Hg diastolic, P less than 0.01) and peripheral vascular resistance (from 2150 +/- 588 to 1207 +/- 345 dyn.sec.cm-5, P less than 0.01). Cardiac output increased in all six. The other 12 patients, 3 of whom had a history of hypertension, had significant increases in cardiac output and systolic blood pressure (from 119 +/- 13 to 127 +/- 7 mm Hg, P less than 0.05) after pericardiocentesis, whereas peripheral vascular resistance decreased. Both groups had similar degrees of cardiac tamponade, as indicated by measurements of cardiac output and intrapericardial, right atrial, and pulmonary-artery wedge pressures. CONCLUSIONS. Elevated blood pressure may occur in some patients with cardiac tamponade who have preexisting hypertension. Moreover, blood pressure may fall after pericardiocentesis in patients who have elevated blood pressure associated with tamponade.     

Quantitative relationship between structure and mutagenic activity in a series of 5-nitroimidazoles

The mutagenic activity of 20 5-nitroimidazoles was tested in Salmonella typhimurium TA-100 strain by means of the Ames test. A multiple regression analysis using the interaction term MR2 X Hb and the chromatographic Rm values yielded the equation: (formula see text); where C is the molar concentration (1 M X 10(-6) of each drug increasing the revertants by five times in the Ames test. The interaction term MR2 X Hb takes into account the positive effect exerted by substituents characterized by higher molar refractivity (MR2) and capable of hydrogen bonding (Hb). It was found that when the electroreduction potentials (EIc.p.) were included, the correlation was not improved.     

Fc epsilon receptors on rat B-lymphocytes: specificity and binding kinetics

The binding kinetics of radiolabelled rat IgE to Fc epsilon receptors (R) of rat B-cells have already been studied in IgE-stimulated animals. The receptors expressed after Nippostrongylus brasiliensis infection or 2 injections of 5 mg IgE/100 g body wt were class-specific: IgE binding was not hindered by rat IgM, IgD, IgA, IgG1, IgG2a, IgG2b and IgG2c in immunocompetitive-binding assays. The rat B-cell Fc epsilon R were not species-specific, since mouse IgE competes with rat IgE for binding to these receptors. The apparent number of Fc epsilon R on rat mesenteric lymph node B-cells varied with temp and was 1.1-2.4 X 10(5) at 4 degrees C and 5.9-7.7 X 10(5) at 37 degrees C. The experimental Ka was not influenced by temp and had an average value of 1.38 X 10(8) M-1. At 4 degrees C the IgE binding to B-cell Fc epsilon R had an association rate of 4.9 X 10(3) M-1 sec-1 and a dissociation rate of 4.65 X 10(-5) sec-1. After a very strong stimulation produced by injecting 5 mg IgE/100 g body wt every 24 hr for 5 days, the equilibrium binding curve became diphasic, indicating a probable heterogeneity of the B-cell Fc epsilon R.     

Determination of the effects of pulmonary arterial hypertension and therapy on the cardiovascular system of rats by impedance cardiography

Aim

To evaluate the effects of bosentan, sildenafil, and combined therapy on the cardiovascular system using impedance cardiography (ICG) in rats with monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH).

Methods

Seventy male Wistar-albino rats were randomized into five groups. A single dose of MCT was given to all rats, except to the control group. After 4 weeks, bosentan, sildenafil, and combined treatment was started and lasted for 3 weeks. The last group that developed PAH did not receive any medication. Echocardiographic evaluation was performed to determine the PAH development. Thoracic fluid content index (TFCI), stroke volume index (SI), heart rate (HR), cardiac index (CI), and myocardial contractility index (IC) were determined. All procedures were performed at the baseline and after 4 and 7 weeks.

Results

Echocardiographic parameters showed that the all MCT-injected rats developed PAH. There were no significant inter- and intra-group differences in TFCI, SI, and IC (P > 0.05), but at the 7th week, CI value in the sildenafil-treated PAH rats was significantly higher than in other groups and HR of PAH rats with combined therapy was significantly lower than in other groups.

Conclusion

PAH did not have an effect on LV function of rats, or if it did, the effect was compensated by physiological processes. Also, sildenafil treatment deteriorated the LV cardiac index.Pulmonary arterial hypertension (PAH) is a chronic lung disease characterized by increased pulmonary artery pressure, pulmonary vascular damage, and medial hypertrophy of pulmonary arterioles, leading to right ventricular (RV) hypertrophy, RV failure, and eventually death (1). The monocrotaline (MCT)-induced model of PAH is the most used model in rats. MCT is a pyrrolizidine alkaloid from the plant Crotalaria spectabilis. A single injection of MCT results in injury to the vascular endothelium of the lung, pulmonary hypertension, and RV hypertrophy and failure within 3 or 4 weeks (2-5).A key feature of PAH is deregulation of important vasodilatory mechanisms in the pulmonary circulation, including increased expression of phosphodiesterase 5 (PDE5) (6). Acute and chronic experimental models of PAH use PDE5 inhibitor sildenafil to reduce pulmonary pressure (7,8). Another important PAH treatment method is by endothelin (ET) receptor antagonist bosentan (9). The endothelin system is highly active in PAH and causes sustained vasoconstriction of pulmonary arteries. It increases the autogenic activity of smooth muscle cells and fibroblasts in the pulmonary vessel wall, thereby decreasing the lumen of pulmonary vessels and also contributing to increased pulmonary vascular resistance (10,11). It is also known that ET receptor expression in the RV myocardium increases due to PAH (12).Heart failure due to PAH can be identified by clinical symptoms that are linked to hemodynamic indices of right heart failure (3,13). Because of the major differences between left and right heart hemodynamics and potentially different responses to pressure overload, the data obtained for RV myocardium do not have to be applicable to the left ventricle (LV). In addition, although chronic pulmonary hypertension selectively overloads the RV, there also manifests LV dysfunction (14). However, hemodynamic indices of the left heart and treatment effects on them cannot be identified in this situation. The aim of this study is to evaluate the effects of PAH and bosentan, sildenafil, and combined treatments on the LV hemodynamic parameters by impedance cardiography (ICG) in rats with MCT-induced PAH.     

Electrical resistances of cultured bovine arterial endothelium in solutions of various resistivities.

Relationships between the electrical resistance (Rm) of cultured endothelium and the resistivity (rho) of the bathing solution have been investigated, using eight monolayers of bovine arterial endothelium. Bathing solutions of differing rho were prepared by mixing culture medium and isosmolar (290 mM) sucrose in various proportions. Relationships between 1/Rm and 1/rho were linear, as predicted, with a mean 1/Rm intercept of zero. The slopes of the relationships give a mean fractional area per unit path length (Ap/delta chi) of 12.7 cm-1 for the paracellular pathways of the cultured endothelium. This resembles previous estimates of Ap/delta chi for mammalian endothelium in arteries. The 1/Rm intercept of zero indicates that the major electrical conducting pathways of cultured arterial endothelium are paracellular.