Pulmonary Venous Resistance Research Articles

The impact of nebivolol, carvedilol and propranolol on pulmonary microhemodynamics in case of experimental pulmonary thromboembolism in rabbits

BACKGROUND: Beta-adrenoblockers nebivolol, carvedilol and propranolol are used in clinical cardiology for the treatment of patients with ischemic heart disease. Pulmonary thromboembolism can develop in such patients. However, its unknown, what will be the pulmonary microcirculatory changes in case of pulmonary thromboembolism after pretreatment with beta-blockers.
 AIM: The comparative analysis of the pulmonary microhemodynamics changes following experimental pulmonary thromboembolism in rabbits after pretreatment with nebovolol, carvedilol and propranolol.
 MATERIAL AND METHODS: In 35 isolated perfused rabbit lungs we investigated the changes of pulmonary microcirculation in case of experimental pulmonary thromboembolism after pretreatment with 1-blocker nebivolol, combined blocker of 1- and 1, 2-adrenoceptors carvedilol, and blocker of 1, 2-adrenoceptors propranolol.
 RESULTS: After administration of 1, 2-adrenoceptors blocker propranolol and 1-blocker nebivolol the most of the pulmonary microcirculatory parameters increased. Combined 1-, 1, 2-blocker carvedilol caused mainly vasodilatory effects of the pulmonary arterial vessels, however, the pulmonary venous resistance increased. Pulmonary thromboembolism after pretreatment with beta-blockers caused pronounced increase of pulmonary artery pressure, precapillary and pulmonary vascular resistance. In that case after pretreatment with carvedilol capillary filtration coefficient was increased two times more than after propranolol administration; after pretreatment with nebivolol capillary filtration coefficient increased less, than after propranolol administration.
 CONCLUSIONS: Acute pulmonary embolism caused less pronounced increasing of capillary filtration coefficient in case of nebivolol administration, than after pretreatment with carvedilol and propranolol.

Lumped parameter models for two-ventricle and healthy and failing extracardiac Fontan circulations.

Fontan circulations are surgical strategies to treat infants born with single ventricle physiology. Clinical and mathematical definitions of Fontan failure are lacking, and understanding is needed of parameters indicative of declining physiologies. Our objective is to develop lumped parameter models of two-ventricle and single-ventricle circulations. These models, their mathematical formulations and a proof of existence of periodic solutions are presented. Sensitivity analyses are performed to identify key parameters. Systemic venous and systolic left ventricular compliances and systemic capillary and pulmonary venous resistances are identified as key parameters. Our models serve as a framework to study the differences between two-ventricle and single-ventricle physiologies and healthy and failing Fontan circulations.

Changes in Pulmonary Circulation in Experimental Model of Pulmonary Thromboembolism after Carvedilol Treatment

In experiments on isolated perfused rabbit lungs, we studied changes in the pulmonary microcirculation in response to carvedilol injection and after modelling pulmonary thromboembolism under conditions of α1- and β1,2-adrenoceptor blockade with this drug. Carvedilol had mainly vasodilator effects on the pulmonary arterial vessels; the pulmonary venous resistance increased and the capillary filtration coefficient remained unchanged under these conditions. In case of pulmonary thromboembolism against the background of carvedilol treatment, the increase in precapillary resistance and the capillary filtration coefficient was more pronounced that in the control, but the postcapillary resistance increased to a lesser extent. The increase in the capillary filtration coefficient is a result of elevated precapillary resistance and enhanced endothelial permeability.

Increased Pulmonary Venous Resistance in the Critically Ill Patients

Increased Pulmonary Venous Resistance in the Critically Ill Patients

Mechanical versus humoral determinants of brain death-induced lung injury.

BackgroundThe mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations.MethodsBrain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury.ResultsIntracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score.ConclusionsBrain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone.

Change in pulmonary blood volume changes pulmonary artery systolic storage

BackgroundA fraction of right ventricular stroke volume (pulmonary artery systolic storage, [PASS]), which is stored in pulmonary arteries during systole and then discharged to the capillaries, determines the diastolic pulmonary capillary blood flow and hence the capillary blood volume participating in gas diffusion. Possibility that increases in pulmonary blood volume (PBV) increase PASS, leading to an improved distribution of ventilation-to-perfusion ratios (V/Q ), was examined. Methods and resultsIncluded were 34 obese patients undergoing bariatric surgery. We used a nitrous oxide-airway-pneumotachographic method to measure PASS. The measurements were repeated before and after increasing PBV. In 20 patients, PBV was increased with infusion of crystalloids, which was guided by pulmonary capillary wedge pressure (PCWP). There was a good correlation between change in PASS and change in PBV (r2 = 0.741, P < 0.0001). However, when the baseline PASS was high, changes in PASS were much less. In patients with a pulmonary artery diastolic-pulmonary capillary wedge pressure gradient ≥6 mmHg, the baseline PASS was correlated with pulmonary venous resistance (r2 = 0.644, P = 0.017). In 14 patients, in whom PBV was increased with both changes in position and infusion of crystalloids, the physiologic dead space-to-tidal volume ratio (VD/VT) was measured as an index of the distribution of V/Q. There was a good negative correlation between PASS and VD/VT (r2 = 0.697, P < 0.0001). However, at a high baseline PASS, increases in PBV decreased PASS (P = 0.0006) and increased VD/VT (P = 0.0018). ConclusionsChanges in PBV change PASS and thereby the distribution of V/Q, depending on pulmonary venous resistance, which determines the baseline PASS.

Increased Pulmonary Venous Resistance in Morbidly Obese Patients Without Daytime Hypoxia

Increased Pulmonary Venous Resistance in Morbidly Obese Patients Without Daytime Hypoxia

Increased Pulmonary Venous Resistance in Morbidly Obese Patients without Daytime Hypoxia

The pulmonary artery (PA) diastolic-pulmonary capillary wedge pressure (PAD-PCWP) gradient has been shown to be increased in morbidly obese patients without daytime hypoxia. In sepsis, the increased pulmonary venous resistance (PvR) contributes to increases in PAD-PCWP gradient. In addition, the obesity-related endotoxemia is known to be involved in the pathophysiology of metabolic syndrome in obesity. Therefore, it is possible that the increased PvR contributes to increases in PAD-PCWP gradient in morbid obesity. We examined this possibility. Included were 25 obese patients without daytime hypoxia undergoing bariatric surgery under general anesthesia. PvR was calculated as the difference between mean PA output pressure and PCWP divided by cardiac index. Mean PA output pressure was computed from the harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA pressure and PCWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and PvR, the PvR/TPVR ratio was used. There was a good correlation between PvR/TPVR ratio and PAD-PCWP gradient (r2=0.785, P<0.0001). When patients were divided into two groups based on PAD-PCWP gradient, the PvR/TPVR ratio was 0.67+/-0.06 (mean+/-SD) in the group with a PAD-PCWP gradient of at least 6 mmHg and 0.48+/-0.05 in the other group (P<0.0001). A strong correlation between PvR/TPVR ratio and PAD-PCWP gradient suggests that the increased PvR contributes to increased PAD-PCWP gradient in obese patients without daytime hypoxia.

Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome

Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome

Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome

Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic-Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome

Increased Pulmonary Venous Resistance Contributes to Increased Pulmonary Artery Diastolic–Pulmonary Wedge Pressure Gradient in Acute Respiratory Distress Syndrome

Pulmonary artery diastolic (PAD)-pulmonary wedge pressure (PWP) gradient has been shown to be increased in sepsis and acute respiratory distress syndrome (ARDS). Because pulmonary venous vasoconstriction induced by endotoxemia in sepsis or postcapillary leukocyte aggregation in ARDS or both can increase pulmonary venous resistance (Rpv), it is possible that the elevated Rpv increases PAD-PWP. The authors examined this possibility by assessing the correlation between Rpv and PAD-PWP gradient in patients with ARDS. Included were 20 patients with ARDS who required surgical procedures during general anesthesia. Rpv was calculated as the difference between mean pulmonary artery (PA) output pressure and PWP divided by cardiac index. Mean PA output pressure was computed from harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA input pressure and PWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and Rpv, the relative pulmonary venous resistance (Rpv/TPVR) was used. There was a good correlation between Rpv/TPVR and PAD-PWP gradient (R = 0.698, P < 0.0001). When patients were classified into two groups based on PAD-PWP gradient, the Rpv/TPVR was 0.66 +/- 0.06 in the group with a PAD-PWP gradient of 6 mmHg or greater and 0.46 +/- 0.08 in the other group (P < 0.0001). A strong correlation between Rpv/TPVR and PAD-PWP gradient suggests that the increased Rpv contributes to increased PAD-PWP gradient in patients with ARDS.

Importance of hypoxic vasoconstriction in maintaining oxygenation during acute lung injury.

To investigate the role of hypoxic pulmonary vasoconstriction in the intrapulmonary blood flow redistribution and gas exchange protection during oleic acid acute lung injury. Prospective, controlled animal study. Research laboratory of an academic institution. Three groups of five mongrel dogs. Induction of acute lung injury by 0.08 mL/kg oleic acid intravenously. Hypoxic pulmonary vasoconstriction inhibition by Escherichia coli endotoxin microdose (15 microg/kg) pretreatment or by metabolic alkalosis (pH 7.60). Pulmonary arterial and venous resistances were determined by flow-pressure curves and by capillary pressure estimation. Regional lung water and pulmonary blood flow were assessed by positron emission tomography. Oleic acid alone increased the arterial and venous resistances, redistributed blood flow away from edematous areas, and decreased the Pao2 from 507 +/- 16 to 373 +/- 60 torr. on Fio2 1.0 and positive end-expiratory pressure 5 cm H2O. Endotoxin pretreatment inhibited the increase in arterial resistance, suppressed the redistribution, and decreased the Pao2 to 105 +/- 22 torr. Alkalosis inhibited the increase in arterial and venous resistances, suppressed the redistribution, and decreased the Pao2 to 63 +/- 12 torr. Reversal of the alkalosis increased the arterial and venous resistances, restored the perfusion redistribution, and improved the Pao2 to 372 +/- 63 torr. Changes in blood gases conformed to predictions of a computer lung model in which hypoxic pulmonary vasoconstriction was suppressed by endotoxin and alkalosis. We conclude that in oleic acid-induced lung injury, a) pulmonary hypertension results from increases in both arterial and venous resistances; b) the increase in arterial resistance is the primary mechanism responsible for the perfusion redistribution and the gas exchange protection; and c) the increase in arterial resistance is most consistent with hypoxic pulmonary vasoconstriction.

Hypoxia and cold stress on pulmonary venous obstruction.

Hemodynamic changes induced by hypoxia and cold stress were examined on the model of pulmonary venous obstruction (PVO) to investigate the mechanism of pulmonary hypertensive crisis. Bilateral pulmonary venous stenosis was surgically created in 7 newborn piglets of the PVO group. Sham operations were performed on 6 piglets of the control group. Following the baseline hemodynamic measurement (FiO2 = 0.3) at 8 weeks after the operation, the piglets were exposed to hypoxia (FiO2 = 0.14) for 10 minutes, and were also exposed to cold stress for 20 minutes. Hypoxia significantly increased mean pulmonary arterial pressure in the PVO group. Hypoxia increased not only pulmonary arterial resistance, but also pulmonary venous resistance in the PVO group. Cold stress did not change pulmonary arterial resistance or pulmonary venous resistance in each group. In the lungs of the PVO group, the medial muscular layer of the pulmonary arteries and pulmonary veins were thickened. This probably accelerates hypoxia-induced vasoconstriction, which in turn increases pulmonary arterial and venous resistances.

Effect of protein kinase C inhibition on hypoxic pulmonary vasoconstriction.

The current study was done to test the hypothesis that protein kinase C (PKC) inhibitors prevent the increase in pulmonary vascular resistance and compliance that occurs in isolated, blood-perfused dog lungs during hypoxia. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Hypoxia significantly increased pulmonary arterial resistance, pulmonary venous resistance, and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The nonspecific PKC inhibitor staurosporine (10(-7) M), the specific PKC blocker calphostin C (10(-7) M), and the specific PKC isozyme blocker Gö-6976 (10(-7) M) inhibited the effect of hypoxia on pulmonary vascular resistance and compliance. In addition, the PKC activator thymeleatoxin (THX; 10(-7) M) increased pulmonary vascular resistance and compliance in a manner similar to that in hypoxia, and the L-type voltage-dependent Ca(2+) channel blocker nifedipine (10(-6) M) inhibited the response to both THX and hypoxia. These results suggest that PKC inhibition blocks the hypoxic pressor response and that the pharmacological activation of PKC by THX mimics the hypoxic pulmonary vasoconstrictor response. In addition, L-type voltage-dependent Ca(2+) channel blockade may prevent the onset of the hypoxia- and PKC-induced vasoconstrictor response in the canine pulmonary vasculature.

Potassium channels modulate canine pulmonary vasoreactivity to protein kinase C activation.

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to protein kinase C (PKC) activation was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. The PKC activators phorbol 12-myristate 13-acetate (PMA; 10(-7) M) and thymeleatoxin (THX; 10(-7) M) significantly increased pulmonary arterial and pulmonary venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. The Ca2+-activated K+-channel blocker tetraethylammonium ions (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) potentiated the pressor response to both PMA and THX on the arterial and venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim (10(-5) M) attenuated the vasoconstrictor effect of PMA and THX on both the arterial and venous vessels. In addition, membrane depolarization by 30 mM KCl elicited an increase in the pressor response to PMA. These results indicate that pharmacological activation of PKC elicits pulmonary vasoconstriction. Closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels as well as direct membrane depolarization by KCl potentiated the response to PMA and THX, indicating that K+ channels modulate the canine pulmonary vasoconstrictor response to PKC activation.

Milrinone decreases both pulmonary arterial and venous resistances in the hypoxic dog

We have studied the effect of milrinone on pulmonary vascular resistance (PVR) in dogs with hypoxic pulmonary vasoconstriction (HPV). Using a pulmonary arterial occlusion method, we measured effective pulmonary capillary pressure (Pcap) by which total PVR was partitioned into arterial (PVRa) and venous (PVRv) components. Hypoxic ventilation (FIO2 = 0.11-0.13) produced significant increases in mean pulmonary arterial pressure (PAP) and Pcap (P < 0.01) associated with increases in PVRa and PVRv (P < 0.01). During the hypoxic period, milrinone significantly decreased mean PAP and Pcap (P < 0.01), reflected in decreases in PVRa and PVRv (P < 0.01). The longitudinal distribution of PVR (PVRa/PVRv) remained unchanged throughout the experiment, indicating that HPV occurred equally in the arterial and venous segments and that milrinone-induced vasodilatation occurred equally in both segments. During hypoxia, milrinone did not produce an increase in cardiac output or a decrease in PaO2. Milrinone also produced significant decreases in mean systemic arterial pressure (P < 0.01) and systemic vascular resistance (P < 0.05) to a similar extent to the decreases in mean PAP and PVR, suggesting no selective dilating effect of milrinone on the pulmonary vasculature. These results indicate that in HPV, milrinone decreased the vascular tone of both pulmonary arterial and venous segments without increasing cardiac work or impairing pulmonary oxygenation. This suggests a potential for use in patients suffering from hypoxic pulmonary hypertension.

Potassium channels modulate hypoxic pulmonary vasoconstriction.

The role of Ca2+-activated K+-channel, ATP-sensitive K+-channel, and delayed rectifier K+-channel modulation in the canine pulmonary vascular response to hypoxia was determined in the isolated blood-perfused dog lung. Pulmonary vascular resistances and compliances were measured with vascular occlusion techniques. Under normoxia, the Ca2+-activated K+-channel blocker tetraethylammonium (1 mM), the ATP-sensitive K+-channel inhibitor glibenclamide (10(-5) M), and the delayed rectifier K+-channel blocker 4-aminopyridine (10(-4) M) elicited a small but significant increase in pulmonary arterial pressure. Hypoxia significantly increased pulmonary arterial and venous resistances and pulmonary capillary pressure and decreased total vascular compliance by decreasing both microvascular and large-vessel compliances. Tetraethylammonium, glibenclamide, and 4-aminopyridine potentiated the response to hypoxia on the arterial segments but not on the venous segments and also further decreased pulmonary vascular compliance. In contrast, the ATP-sensitive K+-channel opener cromakalim and the L-type voltage-dependent Ca2+-channel blocker verapamil (10(-5) M) inhibited the vasoconstrictor effect of hypoxia on both the arterial and venous vessels. These results indicate that closure of the Ca2+-activated K+ channels, ATP-sensitive K+ channels, and delayed rectifier K+ channels potentiate the canine pulmonary arterial response under hypoxic conditions and that L-type voltage-dependent Ca2+ channels modulate hypoxic vasoconstriction. Therefore, the possibility exists that K+-channel inhibition is a key event that links hypoxia to pulmonary vasoconstriction by eliciting membrane depolarization and subsequent Ca2+-channel activation, leading to Ca2+ influx.

Positive end-expiratory pressure increases pulmonary venous vascular resistance in patients after coronary artery surgery.

To investigate the effect of positive and-expiratory pressure (PEEP) on the longitudinal distribution of pulmonary vascular resistance in patients immediately after coronary artery bypass grafting. Prospective, intervention study. Postcardiac surgery intensive care unit in a teaching institution. Twenty patients after elective coronary artery bypass grafting. The effect of PEEP on pulmonary circulation, at four different levels (0, 5, 10, and 15 cm H2O), was analyzed in 20 patients. Mean pulmonary arterial pressure, left atrial pressure, pulmonary artery occlusion pressure, and pulmonary capillary pressure were measured at each PEEP level. A model consisting of two resistances in series was used to analyze the effect of PEEP on the pulmonary circulation. The pulmonary vascular resistance for each area (arterial and venous) of the circulation was calculated. Pulmonary vascular resistance increased from 216 +/- 70 dyne.sec/cm5 at a PEEP of 0 cm H2O to 308 +/- 125 dyne.sec/cm5 at a PEEP of 15 cm H2O (p < .001). This increase, however, resulted solely from an increase in the resistance of the venous part of the pulmonary circulation from 66 +/- 29 to 134 +/- 69 dyne.sec/cm5 (p < .001), without any change in pulmonary arterial resistance. PEEP increases pulmonary vascular resistance solely by increasing pulmonary venous resistance. When applying PEEP, changes in pulmonary vascular resistance may impede the resorption of pulmonary edema fluid.

Starling resistor effects on pulmonary artery occlusion pressure in endotoxin shock provide inaccuracies in left ventricular compliance assessments.

Assessment of left ventricular preload and left ventricular compliance changes in septic shock using pulmonary artery occlusion pressure (PAOP) presumes that this pressure accurately reflects left heart filling pressure. We tested the hypothesis that Starling resistor forces render PAOP inaccurate as an index of left heart filling pressure, resulting in misleading assessments of left ventricular compliance changes. Prospective, randomized, controlled study. Large-animal research laboratory at a university. Fourteen anesthetized domestic pigs weighing 20 to 25 kg. Pulmonary artery flotation catheters and systemic arterial catheters were placed via right cervical vessels. The left atrium was directly catheterized for left atrial pressure measurements. Left ventricular end-diastolic diameter was measured using sonomicrometry. Other measured or calculated variables were mean arterial pressure, mean pulmonary arterial pressure, PAOP, pulmonary capillary pressure, and pulmonary arterial and venous resistances. Pigs received endotoxin (0.5 mg/kg i.v. over 30 mins), or an equivalent volume of saline. At t = 60 mins, pigs were resuscitated with lactated Ringer's solution (40 mL/kg over 30 mins). Measurements were taken before and after endotoxin administration, and immediately and 30 mins after lactated Ringer's solution administration. Data were analyzed by two-way analysis of variance (p < or = .05). PAOP, mean pulmonary arterial pressure, and pulmonary capillary pressure increased after endotoxin infusion, while left atrial pressure and left ventricular end-diastolic diameter decreased. Left atrial pressure and left ventricular end-diastolic diameter returned to baseline immediately after lactated Ringer's solution administration, while PAOP remained increased. Pulmonary arterial resistance and pulmonary venous resistance increased after endotoxin administration, with pulmonary venous resistance showing the greater percent increase. Pulmonary venous resistance decreased transiently immediately after lactated Ringer's solution administration. These changes were not observed in the control group. Accordingly, comparisons of PAOP vs. left ventricular end-diastolic diameter, and left atrial pressure vs. left ventricular end-diastolic diameter yielded divergent results. The dissociation between PAOP and left atrial pressure, while left ventricular and -diastolic diameter (preload volume) decreased, and changes in pulmonary venous resistance, are strong evidence for Starling resistor forces (venocompression) rather than active venoconstriction. These data indicate that PAOP overestimates left atrial pressure during endotoxin shock, making it an inaccurate index of left ventricular preload. This overestimation can cause misleading assessments of left ventricular compliance.

Alteration of segmental vascular resistance in the pulmonary circulation of diabetic rats.

Numerous studies have shown that altered plasma glucose and (or) insulin have profound effects on the pulmonary circulation. Recently, we documented diminished pressor responses to the synthetic thromboxane analogue U-46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F2 alpha) following short-term streptozotocin-induced diabetes in rats. However, these earlier studies examined the effects of diabetes on resistance changes across the entire pulmonary vasculature and made no effort to localize the site(s) of any abnormalities. Thus, in the present study we examined segmental pulmonary vascular resistances using the double-occlusion method in isolated, perfused rat lungs 2 weeks after streptozotocin-induced diabetes. Under baseline conditions, total pulmonary vascular resistance (TPVR) did not differ in lungs isolated from control and diabetic animals (0.66 +/- 0.03 vs. 0.85 +/- 0.05 mmHg.mL-1.min-1, respectively (1 mmHg = 133.3 Pa)). However, control animals demonstrated greater arterial (Ra) than venous (Rv) contribution to TPVR (0.43 +/- 0.02 vs. 0.23 +/- 0.02 mmHg.mL-1.min-1, respectively). This relationship was reversed in diabetic animals (Ra = 0.30 +/- 0.02 mmHg.mL-1.min-1; Rv = 0.54 +/- 0.04 mmHg.mL-1.min-1). Following constriction with U-46619 this pattern persisted, although the absolute vasoconstrictor response to the agent was similar in each segment. Likewise, this pattern of resistance was unaffected following dilation of the pulmonary vascular bed with arginine vasopressin. These findings illustrate that pulmonary segmental vascular resistances are altered and, more specifically, that pulmonary venous resistance is selectively increased, 2 weeks following the induction of diabetes.