Adrenergic innervation of the large arteries and veins of the semiarboreal rat snake Elaphe obsoleta

Fluorescence histochemistry was used to study the adrenergic innervation of the large arteries and veins at six points along the body of the semiarboreal rat snake Elaphe obsoleta. Apart from the vessels adjacent to the heart, there was a marked contrast in the density of adrenergic innervation of anterior and posterior systemic arteries and veins. The anterior arteries and veins have little adrenergic innervation in contrast to the extremely dense innervation of the arteries and veins posterior to the heart. The innervation pattern is consistent with known physiological adjustments to gravity and suggests a mechanism for regulating dependent blood flow via sympathetic nerves. In comparison to the posterior systemic arteries, parallel segments of pulmonary artery taken from the same body position of Elaphe contained a much sparser innervation by adrenergic nerves. The sparser innervation can be correlated with less gravitational disturbance in the pulmonary artery, which is relatively short in this and in other arboreal snakes.     

Element content of human umbilical artery and vein in umbilical cord

To elucidate the element content of newborn blood vessels, umbilical arteries and veins in human umbilical cords, which had the advantage of easy sampling, were examined by ICP-AES. Umbilical cords were removed after birth. Mothers’ ages ranged from 26 to 35 yr. It was found that the content of sulfur was the highest in both umbilical arteries and veins, being higher than the content of calcium and phosphorus. With respect of the content of sulfur, calcium, and magnesium, there were significant differences between the arteries and veins.     

Selective type 5 phosphodiesterase inhibition alters pulmonary hemodynamics and lung liquid production in near-term fetal lambs.

Nitric oxide causes dilation of the pulmonary circulation and reduction in net lung liquid production in the fetal lamb, two critical perinatal events. Phosphodiesterase inhibition alone causes similar changes and also enhances the effects of nitric oxide. To better define the cyclic guanosine 5'-monophosphate (GMP) pathway in these events, we studied the effects of a specific phosphodiesterase inhibitor, E4021, on pulmonary arteries and veins isolated from near-term fetal lambs, as well as in intact, chronically instrumented late-gestation fetal lambs. In the in vitro experiments, both pulmonary arteries and veins relaxed to E4021 in a dose-dependent manner, although pulmonary veins were significantly more sensitive to E4021. Pretreatment with N(G)-nitro-l-arginine (L-NNA) abolished this response in arteries but not in veins. In both arteries and veins, pretreatment with beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate blunted relaxations to E4021. In the in vivo experiments, E4021 infusion into either the pulmonary artery or central venous circulation increased pulmonary blood flow and decreased pulmonary vascular resistance, and these responses were blunted by pretreatment with L-NNA. Net lung liquid production, measured by a dye-dilution technique using blue dextran, decreased when E4021 was infused directly into the pulmonary artery and this effect was not altered by L-NNA. There was no effect on lung liquid production when E4021 was infused into the central venous circulation. Taken together, these results suggest that the pulmonary hemodynamic effects of E4021 involve the cyclic GMP pathway and are primarily nitric oxide synthase dependent. In contrast, the effects on E4021 on net lung liquid production appear to be independent of nitric oxide synthase, suggesting that these two critical perinatal events might be modulated independently.     

Cholinesterase-containing nerve fibres on blood vessels in lungs of some laboratory mammals

Summary Distribution of cholinesterase-containing nerve fibres on blood vessels in the lungs of rats, mice, rabbits, guinea pigs, cats, dogs, and rhesus monkeys has been studied with the thiocholine method modified by Coupland and Holmes and with the direct-coloring method according to Karnovsky and Roots. The presence of acetylcholinesterase positive nerve fibres on the pulmonary arteries has been established only in four species of the studied animals, namely the cat, the dog, the rhesus monkey and the rabbit. These nerves form d distinct plexus on the border between the media and adventitia. In the thick walled perihilar branches of the pulmonary artery of the rabbit the nerve fibres penetrate—as a rule—into the outer half of the media. Despite many times repeated experiments and careful investigations no nerve fibres have been found on the intrapulmonary branches of the blood vessels in the lungs of rats, mice, and guinea pigs. In the walls of the pulmonary veins, with the exception of the pulmonary veins in the rat and the mouse, cholinesterase fibres have been identified only seldom. Acetylcholinesterase nerve fibres in medio-adventitial localization have also been found in the walls of bronchial arterioles, this being the case in all the species under study. Bronchial veins do not exhibit any nerve fibres. The distribution of the acetylcholinesterase-containing nerve fibres on the pulmonary arteries is different from species to species.     

Differential effects of prostaglandins A1 and A2 on pulmonary vascular resistance in the dog.

The effects of PGA1 and PGA2 were studied in the canine pulmonary vascular bed. Infusion of PGA1 into the lobar artery decreased lobar arterial and venous pressure but did not change left atrial pressure. In contrast, PGA2 infusion increased lobar arterial and venous pressure and the effects of this substance were similar in experiments in which the lung was perfused with dextran or with blood. These data indicate that under conditions of controlled blood flow PGA1 decreases pulmonary vascular resistance by dilating intrapulmonary veins and to a lesser extent vessels upstream to the small veins, presumably small arteries. The present data show that PGA2 increases pulmonary vascular resistance by constricting intrapulmonary veins and upstream vessels. The predominant effect of PGA2 was on upstream vessels and the pressor effect was not due to interaction with formed elements in the blood or platelet aggregation.     

Vasoactive intestinal polypeptide-immunoreactive nerves in the pulmonary vasculature of the aquatic file snake Acrochordus granulatus

Summary The indirect immunofluorescence technique was used to determine the distribution of vasoactive intestinal polypeptide-immunoreactive and somatostatin-immunoreactive axons in the pulmonary vasculature of the aquatic file snake Acrochordus granulatus. A dense distribution of vasoactive intestinal polypeptide-immunoreactive axons was found on the common pulmonary artery, the anterior and posterior pulmonary arteries, and the smaller arteries branching to the lung. The density of these axons appeared greater in arterial preparations taken from more distal regions of the lung. The densest distribution of vasoactive intestinal polypeptide-immunoreactive axons was observed on the larger pulmonary veins in all regions of the lung. These axons were observed on the larger veins within the lung parenchyma but not on the smaller veins. Axons and cell bodies were observed in the vagal nerve trunks which run parallel to the pulmonary arteries and veins. In contrast, no somatostatin-immunoreactive axons were observed in any region of the pulmonary vasculature. It is proposed that the perivascular plexus of vasoactive intestinal polypeptide-immunoreactive axons may represent part or all of the vagal postganglionic innervation of the pulmonary vasculature.     

Diameter and flow velocity changes in small pulmonary vessels due to microembolization

The pulmonary vascular bed was embolized with glass beads in small doses that induced no significant changes in pulmonary arterial pressure in anesthetized cats. We analyzed changes in internal diameter (ID), flow velocity, and volume flow of embolized and nonembolized arteries simultaneously with ID changes of small veins. In embolized arteries, with 180-, 300-, and 500-microns beads, ID constricted maximally in just proximal portions of the plug by 22, 23, and 17%, respectively, but with 840-microns beads, no ID constriction occurred. With 50-microns beads, the maximum ID constriction occurred in arteries of 200-300 microns but not in those of 100-200 microns. The constriction decreased in the upstream larger arteries and disappeared in those greater than 800 microns ID. In the nonembolized arteries no ID change occurred. Veins constricted slightly compared with arteries. By heparin pretreatment, ID constriction was slightly attenuated in arteries and was almost abolished in veins, whereas it was not affected with hexamethonium bromide. At a branching site, volume flow to an embolized artery decreased because of a decrease in ID and flow velocity, whereas volume flow to a nonembolized artery increased because of an increase in flow velocity. We concluded that pulmonary microembolization induced a vasoconstriction chiefly in small pulmonary arteries upstream to the plug. After embolization, blood flow was locally redistributed from an embolized to a nonembolized artery at a branching site. Arterial vasoconstriction may be mediated chiefly by local mechanical factors.     

Parathyroid hormone-related protein-mediated responses in pulmonary arteries and veins of newborn lambs

PTHrP has important roles in lung development and function. Here we determined the vasomotor responses of isolated pulmonary arteries and veins of newborn and adult sheep to PTHrP. In vessels constricted with endothelin-1, PTHrP (PTHrP 1-34) caused greater relaxation of veins than of arteries. In both vessel types, relaxation to the peptide was less in adult than in newborn vessels. In newborn lambs, PTHrP-induced relaxation was not affected by endothelium removal, inhibition of eNOS, or inhibition of adenylyl cyclases by SQ-22536. However, relaxation was attenuated by 4-aminopyridine, inhibitor of voltage-dependent potassium channels, in both arteries and veins, and by charybdotoxin, inhibitor of calcium-activated potassium channels, in veins. When vessels were saturated with 8-BrcAMP (3 x 10(-4) M), to eliminate relaxation mediated by endogenous cAMP, PTHrP-induced relaxation was partially attenuated. In vessels treated with 8-BrcAMP (3 x 10(-4) M), 4-aminopyridine but not charybdotoxin inhibited relaxation induced by PTHrP 1-34 in both arteries and veins. Radioimmunoassay showed that, in the presence of a general phosphodiesterase inhibitor, PTHrP caused a concentration-dependent increase in intracellular cAMP content in arteries and veins, which was largely abolished by SQ-22536. Our results demonstrate that PTHrP is a potent vasodilator of pulmonary vessels, with a greater effect in veins than in arteries. Relaxation induced by the peptide contains both cAMP-dependent and -independent components. In both arteries and veins, voltage-dependent potassium channels mediate the response to PTHrP, at least in part, in a cAMP-independent fashion; and in veins, calcium-activated potassium channels may be stimulated by elevated cAMP levels.     

Effect of respiratory gases on compliance of intrapulmonary arteries and veins

A method was developed that permitted changes in the pressure-volume characteristics of large intrapulmonary vessels occurring with changes in the composition of alveolar gas to be studied in excised lungs. The capillary bed was emptied by keeping intravascular pressure well below alveolar pressure, and the relationship between changes in the volume of the pulmonary arteries or veins with changes in transpulmonary pressure was measured. The volume of the arteries and veins always decreased with a decrease in transpulmonary pressure, but when the alveoli contained carbon dioxide, the decrease in vascular volume was less, for the same decrease in transpulmonary pressure, than when the alveoli contained oxygen or nitrogen without carbon dioxide. This change with carbon dioxide was probably due to a decrease in the compliance of the larger intrapulmonary arteries and veins. Since there was no pathway for carbon dioxide to enter these vessels except by diffusion from the alveoli, it is concluded that carbon dioxide can act directly on the intrapulmonary arteries and veins to reduce their compliance, but it is not known whether this effect has physiological significance. No effect on the large pulmonary vessels was found with variations in alveolar concentrations of oxygen. blood vesselsblood volumecarbon dioxidediffusionlungspulmonary circulation     

Structural and functional characteristics of the special regulatory devices in the peripheral pulmonary circulation in rabbits

The present study intended to describe in detail the several blood vessels harboring special regulatory devices in rabbit’s pulmonary tissue using light and electron microscopy and immuno-histochemistry. Numerous throttle arteries were recorded within the adventitia of the segmental and sub-segmental bronchi and within pulmonary pleura. These arteries showed characteristic narrow or obliterated lumens and some of them bear longitudinal muscular intimal bolsters. For the first time, TEM revealed some structural modifications of the vascular endothelial cells of these arteries indicating that they become more activated to perform some additional functions. Arteriovenous anastomoses (AVAs) including direct shunt vessels and glomus organs were also recognized. Direct arteriovenous shunts appeared as small connecting devices communicating between small arteries and small veins while glomus organs consisted of the tortuous glomus vessels and the related afferent and efferent vessels. Several arteries and veins showing unique unusual structural characteristics were also described. For the first time, serotonin (5-HT) was strongly expressed in the vascular endothelium and muscle fibers of throttle arteries, in glomus cells of the glomus vessels, and in vascular endothelium of some veins and venules of special structure. The exact role of 5-HT is still unknown and further investigations are required to determine the types and distribution of 5-HT receptors present in these vascular devices. We concluded that these special vascular devices can play a critical role in controlling blood flow and pressure in the peripheral pulmonary circulation; however, the exact physiological mechanisms by which they work or are controlled remain unknown providing a ripe area for further investigation.     

Increased substance P content in nerve fibers associated with mesenteric veins from deoxycorticosterone acetate (DOCA)-salt hypertensive rats

This study examined sensory nerves associated with mesenteric arteries and veins in sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Reactivity of arteries and veins to substances released from sensory nerves was also studied in vitro using computer-assisted video microscopy. Co-localization of substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactivity (ir) was used to evaluate perivascular sensory nerves. Radioimmunoassay was used to quantify SP- and CGRP-ir content. Immunohistochemical studies revealed a plexus of SP/CGRP-ir nerves associated with arteries and veins. The intensity of SP-ir, but not CGRP-ir labeling was greater in arteries and veins from DOCA-salt compared to sham rats. RIA measurements revealed that the CGRP-ir content of arteries and veins was higher than the SP-ir content but there was a significant increase in SP-ir, but not CGRP-ir, content in arteries and veins from DOCA-salt rats. SP (0.03-1 microM) contracted veins and the NK-3 receptor agonist, senktide, mimicked this effect. There were no differences in SP or senktide reactivity of veins from sham or DOCA-salt rats. SP, but not senktide, relaxed KCl (40 mM) preconstricted arteries. CGRP (0.3 microM), acetylcholine (10 microM) and capsaicin (1 microM) relaxed KCl-preconstricted arteries and veins. The NK-1 receptor agonist, substance P methyl ester relaxed arteries but not veins. These data indicate that DOCA-salt hypertension is associated with upregulation of SP content in perivascular nerves. NK-3 receptors mediate venoconstriction which is unchanged in DOCA-salt hypertension. Increased release of SP from perivenous nerves might contribute to the increased venomotor tone in DOCA-salt hypertension.     

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ET(A) antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ET(A) antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ET(A)-mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension.     

Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions

Pulmonary veins show greater sensitivity to endothelin (ET)-1-induced vasoconstriction than pulmonary arteries, and remodeling was observed in pulmonary veins under hypoxic conditions. We examined, using an immunohistochemical method, the expression of Big ET-1, ET-converting enzyme (ECE), and ET(A) and ET(B) receptors in rat pulmonary veins under normoxic and hypoxic conditions. In control rats, Big ET-1 and ECE were coexpressed in the intima and media of the pulmonary veins, with an even distribution along the axial pathway. ET(A) and ET(B) receptors were expressed in the pulmonary veins, with a predominant distribution in the proximal segments. The expression of Big ET-1 was more abundant in the pulmonary veins than in the pulmonary arteries. After exposure to hypoxia for 7 or 14 days, the expression of Big ET-1, ECE, and ET receptors increased in small pulmonary veins. Increases in the medial thickness, wall thickness, and immunoreactivity for alpha-smooth muscle actin were also observed in the small pulmonary veins under hypoxic conditions. The upregulation of ET-1 and ET receptors in the small pulmonary veins is associated with vascular remodeling, which may lead to the development of hypoxic pulmonary hypertension.     

The adrenergic innervation of arteries and veins in rats with DOCA-NaCl hypertension: the role of sodium and chloride overload

The adrenergic innervation of major arteries and veins was examined in DOCA-NaCl hypertensive rats using a histochemical fluorescent technique to detect the intraneuronal catecholamine content. The possible role of sodium and chloride ions was studied in DOCA-treated rats which were fed a low-salt diet which was supplemented with sodium bicarbonate instead of sodium chloride. Focal defects of adrenergic innervation were observed in blood vessels of DOCA-NaCl hypertensive rats. Nevertheless, the degree of these changes differed according to the vascular bed examined. A maximum decrease of the catecholamine content in varicosities of adrenergic terminals was found in the femoral vessels while there were nearly no changes in tail arteries and veins. Adrenergic innervation was usually more impaired in veins than in corresponding arteries of hypertensive animals. Pronounced changes in blood vessels of rats with DOCA-NaCl hypertension contrasted with the maximum alterations observed in those hypertensive DOCA-treated animals which were fed a NaHCO3-supplemented diet. Thus a chloride overload seems to be more important for alteration of adrenergic innervation than the degree of blood pressure elevation or the sodium overload per se.     

Cardiovascular agents affect the tone of pulmonary arteries and veins in precision-cut lung slices

Introduction

Cardiovascular agents are pivotal in the therapy of heart failure. Apart from their action on ventricular contractility and systemic afterload, they affect pulmonary arteries and veins. Although these effects are crucial in heart failure with coexisting pulmonary hypertension or lung oedema, they are poorly defined, especially in pulmonary veins. Therefore, we investigated the pulmonary vascular effects of adrenoceptor agonists, vasopressin and angiotensin II in the model of precision-cut lung slices that allows simultaneous studies of pulmonary arteries and veins.

Materials and Methods

Precision-cut lung slices were prepared from guinea pigs and imaged by videomicroscopy. Concentration-response curves of cardiovascular drugs were analysed in pulmonary arteries and veins.

Results

Pulmonary veins responded stronger than arteries to α₁-agonists (contraction) and β₂-agonists (relaxation). Notably, inhibition of β₂-adrenoceptors unmasked the α₁-mimetic effect of norepinephrine and epinephrine in pulmonary veins. Vasopressin and angiotensin II contracted pulmonary veins via V_1a and AT₁ receptors, respectively, without affecting pulmonary arteries.

Discussion

Vasopressin and (nor)epinephrine in combination with β₂-inhibition caused pulmonary venoconstriction. If applicable in humans, these treatments would enhance capillary hydrostatic pressures and lung oedema, suggesting their cautious use in left heart failure. Vice versa, the prevention of pulmonary venoconstriction by AT₁ receptor antagonists might contribute to their beneficial effects seen in left heart failure. Further, α₁-mimetic agents might exacerbate pulmonary hypertension and right ventricular failure by contracting pulmonary arteries, whereas vasopressin might not.     

Pulmonary vascular remodelling in a high-altitude Aymara Indian

A histological study of the pulmonary vasculature in a young male high-altitude Aymara Indian revealed four aspects of interest. There was muscularization of the terminal portion of the pulmonary arterial tree to involve pulmonary arterioles as small as 15 m in diameter, thus forming a basis for the slightly increased pulmonary vascular resistance of native highlanders. Intimal longitudinal muscle was found in pulmonary arteries and arterioles and thought to be due to chronic alveolar hypoxia. Inner muscular tubes similar to those found in chronic obstructive lung disease were present. Pulmonary veins and venules also showed intimal muscularization suggesting that alveolar hypoxia affects vascular smooth muscle cells per se irrespective of their situation. The nature of the remodelling in a pulmonary blood vessel depends on a combination of hypoxia and haemodynamics.     

Pharmacological properties of canine intrapulmonary blood vessels

The contractile response of ring segments of large, medium, and small pulmonary arteries and veins of the dog to histamine, norepinephrine, and serotonin have been studied. The maximum contractile response to these drugs was normalized with respect to the maximal response obtained in stimulation with 127 mM K+. The small pulmonary artery was more reactive to histamine, norepinephrine, and serotonin when compared with large and medium pulmonary arteries. The medium and large pulmonary artery showed no difference in reactivity to histamine. However, the mean effective dose (ED50) values for these agonists among the different segments of pulmonary arteries showed no significant difference. The small and medium pulmonary veins demonstrated increased reactivity to histamine, but not norepinephrine and serotonin. The ED50 values also indicated that both small and medium veins were more sensitive to histamine when compared with the large pulmonary vein. The log concentration percent response curves for both small and medium pulmonary veins were displaced leftward (increased sensitivity) with respect to that for the large pulmonary vein. However, the reactivity and sensitivity to histamine between medium and small pulmonary veins were no different. The reactivity and sensitivity of different segments of pulmonary veins to norepinephrine and serotonin showed no significant differences among them. We conclude that histamine and other vasoactive substances, which are directly or indirectly related to mast cell degranulation, exert pharmacological effects on the pulmonary vasculature which possesses differential responsiveness at various levels of the vascular tree.     

Occlusion pressures vs. micropipette pressures in the pulmonary circulation

Because of the discrepancies between the arterial and venous occlusion technique and the micropuncture technique in estimating pulmonary capillary pressure gradient, we compared measurements made with the two techniques in the same preparations (isolated left lower lobe of dog lung). In addition, we also obtained direct and reliable measurements of pressures in 0.9-mm arteries and veins using a retrograde catheterization technique, as well as a microvascular pressure made with the double-occlusion technique. The following conclusions were made from dog lobes perfused with autologous blood at normal flow rate of 500-600 ml/min and pressure gradient of 12 mmHg. 1) The double-occlusion technique measures pressure in the capillaries, 2) a small pressure gradient (0.5 mmHg) exists between 30- to 50-micron arteries and veins, 3) a large pressure gradient occurs in arteries and veins greater than 0.9 mm, 4) the arterial and venous occlusion techniques measure pressures in vessels that are less than 900 microns diam but greater than 50 microns, very likely close to 100 microns, 5) serotonin constricts arteries (larger and smaller than 0.9 mm) whereas histamine constricts veins (larger and smaller than 0.9 mm). Thus three different techniques (small retrograde catheter, arterial and venous occlusion, and micropuncture) show consistent results, confirming the presence of significant resistance in large arteries and veins with minimal resistance in the microcirculation.     

Heterogeneity in responses of isolated monkey arteries and veins to atrial natriuretic peptide

Regional differences in responses of isolated monkey arteries and veins to atrial natriuretic peptide were investigated by recording isometric tension. Addition of atrial natriuretic peptide (4 X 10(-12) to 4 X 10(-8) M) produced a concentration-dependent relaxation in isolated monkey arteries and veins. No significant difference was observed between the responses to rat and human atrial natriuretic peptides. A marked heterogeneity in responses to rat atrial natriuretic peptide, however, was observed in arterial preparations. The decreasing order of the response was as follows: renal greater than pulmonary greater than femoral = mesenteric greater than coronary greater than middle cerebral greater than basilar arteries. A heterogeneity in the relaxation produced by atrial natriuretic peptide was also observed in monkey veins. The decreasing order of the response was as follows: pulmonary greater than mesenteric = portal greater than femoral greater than renal = inferior caval veins. On the other hand, 10(-5) M sodium nitroprusside caused a maximal relaxation in all monkey arteries and veins used. In the middle cerebral, basilar, and coronary arteries, the relaxant effects of rat atrial natriuretic peptide on KCl-induced contraction were significantly smaller than those on the preparations contracted by an agonist such as prostaglandin F2 alpha. These results suggest that there exist profound regional vasorelaxant selectivities of atrial natriuretic peptide in isolated monkey arteries and veins.     

Altered reactivity of pulmonary vessels in postobstructive pulmonary vasculopathy.

Chronic ligation of one pulmonary artery results in pulmonary vascular remodeling and bronchial angiogenesis, collectively known as postobstructive pulmonary vasculopathy (POPV). To investigate pulmonary vascular reactivity in POPV, we ligated the left main pulmonary artery of guinea pigs and, after 1-10 mo, prepared explants by inflating lungs with agarose and sectioning them into approximately 1-mm-thick slices; we measured areas of pulmonary vessels and determined contractile responses to histamine and serotonin (5-HT) and relaxant responses to ACh and sodium nitroprusside. We found maximal contractions of arteries to 5-HT (24. 4 +/- 2.6%) and of veins to histamine (53.9 +/- 4.7%) were significantly increased in POPV of 3-mo duration compared with those of controls (16.8 +/- 1.5 and 40.8 +/- 5.0%, respectively). Relaxation of arteries with ACh was enhanced at 10 mo but not at 1 mo after ligation. Relaxation with sodium nitroprusside was increased in veins at 1 mo after ligation but was not altered in arteries. Morphometry revealed reduced diameters of arteries and veins without increased medial thickness. Our data suggest that the enhanced contractile responses of pulmonary vessels to histamine and 5-HT in POPV were not a result of endothelial dysfunction or of structural alterations but might be caused by as-yet-undiscovered mechanisms.