Altered artery mechanics and structure in monocrotaline pulmonary hypertension

Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model.     

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.     

Pulmonary arterial dilation by inhaled NO: arterial diameter, NO concentration relationship.

The objective of this study was to determine the nitric oxide (NO) concentration and vessel diameter dependence of the pulmonary arterial dilation induced by inhaled NO. Isolated dog lung lobes were situated between a microfocal X-ray source and X-ray detector and perfused with either blood or plasma. Boluses of radiopaque contrast medium were injected into the lobar artery under control conditions, when the pulmonary arteries were constricted by infusion of serotonin and when the serotonin infusion was accompanied by inhalation of from 30 to 960 parts/million NO. Arterial diameter measurements were obtained from X-ray images of vessels having control diameters in the 300- to 3,400-microm range. Serotonin constricted the vessels throughout the size range studied, with an average decrease in diameter of approximately 20%. The fractional reversal of the serotonin-induced constriction by inhaled NO was directly proportional to inhaled NO concentration, inversely proportional to vessel size, and greater with plasma than with blood perfusion in vessels as large as 3 mm in diameter. The latter indicates that intravascular hemoglobin affected the bronchoalveolar-to-arterial luminal NO concentration gradient in fairly large pulmonary arteries. The data provide information regarding pulmonary arterial smooth muscle accessibility to intrapulmonary gas that should be useful as part of the database for modeling the communication between intrapulmonary gas and pulmonary arterial smooth muscle cells in future studies.     

Chronic in ovo hypoxia decreases pulmonary arterial contractile reactivity and induces biventricular cardiac enlargement in the chicken embryo

Although chronic prenatal hypoxia is considered a major cause of persistent pulmonary hypertension of the newborn, experimental studies have failed to consistently find pulmonary hypertensive changes after chronic intrauterine hypoxia. We hypothesized that chronic prenatal hypoxia induces changes in the pulmonary vasculature of the chicken embryo. We analyzed pulmonary arterial reactivity and structure and heart morphology of chicken embryos maintained from days 6 to 19 of the 21-day incubation period under normoxic (21% O(2)) or hypoxic (15% O(2)) conditions. Hypoxia increased mortality (0.46 vs. 0.14; P < 0.01) and reduced the body mass of the surviving 19-day embryos (22.4 +/- 0.5 vs. 26.6 +/- 0.7 g; P < 0.01). A decrease in the response of the pulmonary artery to KCl was observed in the 19-day hypoxic embryos. The contractile responses to endothelin-1, the thromboxane A(2) mimetic U-46619, norepinephrine, and electrical-field stimulation were also reduced in a proportion similar to that observed for KCl-induced contractions. In contrast, no hypoxia-induced decrease of response to vasoconstrictors was observed in externally pipped 21-day embryos (incubated under normoxia for the last 2 days). Relaxations induced by ACh, sodium nitroprusside, or forskolin were unaffected by chronic hypoxia in the pulmonary artery, but femoral artery segments of 19-day hypoxic embryos were significantly less sensitive to ACh than arteries of control embryos [pD(2) (= -log EC(50)): 6.51 +/- 0.1 vs. 7.05 +/- 0.1, P < 0.01]. Pulmonary vessel density, percent wall area, and periarterial sympathetic nerve density were not different between control and hypoxic embryos. In contrast, hypoxic hearts showed an increase in right and left ventricular wall area and thickness. We conclude that, in the chicken embryo, chronic moderate hypoxia during incubation transiently reduced pulmonary arterial contractile reactivity, impaired endothelium-dependent relaxation of femoral but not pulmonary arteries, and induced biventricular cardiac hypertrophy.     

Adrenoceptor function in the bovine pulmonary circulation

The bovine pulmonary vascular response to alpha- and beta-agonists was studied using an awake intact calf model. Pulmonary arterial pressure, pulmonary arterial wedge pressure, left atrial pressure, systemic arterial pressure, and cardiac output were measured in response to 3 min infusions of isoproterenol (beta-agonist; 0.12, 0.24, 0.48, 0.9, and 1.8 micrograms X kg-1 X min-1) and phenylephrine (alpha-agonist, 0.15, 0.30, 0.60, 1.15, and 2.30 micrograms X kg-1 X min-1). Phenylephrine caused an increase in vascular resistance in the pulmonary arterial and venous compartments. The slope of the resistance in response to phenylephrine was greater in the pulmonary arterial than pulmonary venous circulation. Isoproterenol resulted in a dose-dependent decrease in vascular resistance in the pulmonary arteries and veins. The vascular resistance was decreased to the same level in the pulmonary arteries and veins although the arteries showed a greater percent change. In addition, isoproterenol infusion resulted in a transient decrease in arterial pH and increase in values for packed cell volume and haemoglobin.     

Slow and incomplete sympathetic reinnervation of rat tail artery restores the amplitude of nerve-evoked contractions provided a perivascular plexus is present

We have investigated the recovery of sympathetic control following reinnervation of denervated rat tail arteries by relating the reappearance of noradrenergic terminals to the amplitude of nerve-evoked contractions of isometrically mounted artery segments in vitro. We have also assessed reactivity to vasoconstrictor agonists. Freezing the collector nerves near the base of the tail in adult rats denervated the artery from ～40 mm along the tail. Restoration of the perivascular plexus declined along the length of the tail, remaining incomplete for >6 mo. After 4 mo, nerve-evoked contractions were prolonged but of comparable amplitude to control at ～60 mm along the tail; they were smaller at ～110 mm. At ～60 mm, facilitation of contractions to short trains of stimuli by the norepinephrine transporter blocker, desmethylimipramine, and by the α2-adrenoceptor antagonist, idazoxan, was reduced in reinnervated arteries. Blockade of nerve-evoked contractions by the α1-adrenoceptor antagonist, prazosin, was less and by idazoxan greater than control after 8 wk but similar to control after 16 wk. Sensitivity of reinnervated arteries to the α1-adrenoceptor agonist, phenylephrine, was raised in the absence but not in the presence of desmethylimipramine. Sensitivity to the α2-adrenoceptor agonist, clonidine, was maintained in 16-wk reinnervated arteries when it had declined in controls. Thus regenerating sympathetic axons have a limited capacity to reinnervate the rat tail artery, but nerve-evoked contractions match control once a relatively sparse perivascular plexus is reestablished. Functional recovery involves prolongation of contractions and deficits in both clearance of released norepinephrine and autoinhibition of norepinephrine release.     

Vasoactive mediators and pulmonary hypertension after cigarette smoke exposure in the guinea pig.

The pathogenesis of pulmonary hypertension in patients with chronic obstructive pulmonary disease is not understood. We have previously shown increased levels of mediators that control vasoconstriction (endothelin-1), vascular cell proliferation (endothelin-1 and vascular endothelial growth factor), and vasodilation (endothelial nitric oxide synthase) in the intrapulmonary arteries of animals exposed to cigarette smoke. To determine whether these mediators could be implicated in the structural remodeling of the arterial vasculature and increased pulmonary arterial pressure caused by chronic cigarette smoke exposure, guinea pigs were exposed to daily cigarette smoke for 6 mo. Pulmonary arterial pressures were measured. Intrapulmonary artery structure was analyzed by morphometry, artery mediator protein expression by immunohistochemistry, and artery mediator gene expression by laser capture microdissection and real-time RT-PCR. We found that the smoke-exposed animals developed increases in pulmonary arterial pressure and increased muscularization of the small pulmonary arteries. Gene expression and protein levels of all three mediators were increased, and pulmonary arterial pressure correlated both with the levels of mediator production and with the degree of arterial muscularization. We conclude that chronic smoke exposure produces increased vasoactive mediator expression in the small intrapulmonary arteries and that these mediators are associated with vascular remodeling as well as increased pulmonary arterial pressure. These findings support the idea that hypertension in chronic obstructive pulmonary disease is a result of direct cigarette smoke-mediated effects on the vasculature and suggest that interference with endothelin and VEGF production and activity or augmentation of nitric oxide levels may be beneficial.     

Sensitivity and adrenoceptor affinity in the mesenteric artery of the deoxycorticosterone acetate hypertensive rat

This study examines vascular reactivity to alpha-adrenoceptor agonists in mineralocorticoid (deoxycorticosterone acetate (DOCA-salt) hypertensive and normotensive rats. The rats were anesthetized and the mesenteric artery was excised and cut helically into strips that were mounted in a muscle bath for the measurement of isometric force development. Addition of norepinephrine, epinephrine, phenylephrine, methoxamine, or clonidine to the bath caused contractions in all arteries. Arteries from hypertensive rats were more sensitive (lower ED50 values) to each of the agonists than arteries from normotensive rats. alpha-Adrenoceptor affinity for phentolamine (Schild analysis; norepinephrine as the agonist) in hypertensive arteries was not significantly different from that in normotensive arteries. Maximal force generation to clonidine was greater in hypertensive arteries than in normotensive arteries. These results demonstrate an augmented vascular sensitivity to several alpha-adrenoceptor agonists in DOCA hypertensive rats. This change in sensitivity is independent of a change in affinity for the adrenoceptor antagonist, phentolamine. It may be that a change in receptor number or an alteration in a post-receptor activation event accounts for this enhanced adrenoceptor responsiveness in mineralocorticoid hypertension.     

Comparison of mechanical behavior among the extrapulmonary arteries from rats

Results of comparative tests on pulmonary arteries from untreated Long-Evans rats are presented from three sections of the artery: the trunk, and the right and left main extrapulmonary arteries. Analyses were conducted looking for mechanical differences between the flow (longitudinal) and circumferential directions, between the right and left main arteries, and between each of the mains and the trunk. The mechanical properties of rat pulmonary arteries were obtained with a bubble inflation technique. A flat disk of rat pulmonary artery was constrained at the periphery and inflated, and the geometry of the resulting bubble of material recorded from six different angles. To analyze the data, the area under the stress-strain curve was calculated for each test and orientation. This area, related to the strain-energy density, was calculated at stress equal to 200kPa, for the purpose of statistical comparison. The mean values for the area show that the trunk is less compliant than the main arteries; this difference is supported by histological evidence. When comparing the circumferential and longitudinal properties of the arteries, differences are found for the trunk and left main arteries, but with opposite orientations being more compliant. The mean values for the two orientations for the right main artery are statistically identical. There was indication of significant difference in mechanical properties between the trunk and the main arteries. The left main artery in the circumferential orientation is highly compliant and appears to strongly influence the likelihood that significant differences will exist when included in a statistical population. These data show that each section of the extrapulmonary arterial system should not be expected to behave identically, and they provide the baseline mechanical behavior of the pulmonary artery from normotensive rats.     

Biomechanical and morphometric properties of the arterial wall referenced to the zero-stress state in experimental diabetes

Morphometric and passive biomechanical properties were studied in isolated segments of the thoracic and abdominal aorta, left common carotid artery, left femoral artery and the left pulmonary artery in 20 non-diabetic and 28 streptozotocin (STZ)-induced diabetic rats. The diabetic and non-diabetic rats were divided into groups living 1, 4, 8, and 12 weeks after the induction of diabetes (n = 7 for each diabetic group) or sham injection (n = 5 for each group). The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. The vessel diameter and length were obtained from digitized images of the arterial segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state data. The zero-stress state was obtained by cutting vessel rings radially causing the rings to open up into a sector. Diabetes was associated with pronounced morphometric changes, e.g., wall thickness. With respect to the biomechanical data, the opening angle increased and reached a plateau in 4 weeks after which it decreased again (p < 0.05). The opening angle was smallest in the thoracic aorta and largest in the pulmonary artery. Furthermore, it was found that the circumferential stiffness of the arteries studied increased with the duration of diabetes. In the longitudinal direction significant differences were found 8 weeks after injection of STZ in all arteries except the pulmonary artery. In the 12 weeks group, the femoral artery was stiffest in the circumferential direction whereas the thoracic aorta was stiffest in the longitudinal direction. The accumulated serum glucose level correlated with the arterial wall thickness and elastic modulus (correlation coefficient between 0.56 and 0.81).     

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.     

Higher sensitivity of cerebral arteries isolated from premature and newborn baboons to adrenergic and cholinergic stimulation

To find whether effects of adrenergic and cholinergic agents on cerebral artery were dependent on maturity, we examined responses of isolated cerebral artery strips harvested from premature, term newborn and adult baboons. Although cerebral arteries from many species are only mildly sensitive to norepinephrine, we found the perinatal cerebral arteries to be quite responsive to the amine. Cerebral arteries from premature and newborn baboons were significantly (P less than 0.001) more sensitive to norepinephrine than were arteries from adults; medium effective concentration (EC50) for norepinephrine were 3 X 10(-8), 6 X 10(-8) and 32 X 10(-8)M for prematures, newborns and adults, respectively. Arteries showed a similar age-dependence in the sensitivity of the response to phenylephrine, an alpha 1-adrenoceptor agonist. EC50 values for KC1 did not differ among groups, nor did the maximum response to norepinephrine. Arteries from premature and newborn baboons showed marked contractile response to acetylcholine (maximum tensions 5.9 +/- 0.6 and 6.4 +/- 0.8 g/mm2, respectively), whereas arteries from adult baboons showed little response (0.6 +/- 0.1 g/mm2). Arteries from premature and newborn animals showed a more marked relaxation response to isoproterenol than did arteries from adult animals; the degree of relaxation from an induced contraction was 63% (premature), 72% (newborn) and 10% (adult). There was no age-dependence in the relaxation response to sodium nitrite. We conclude that the events coupling alpha 1, beta or muscarinic receptor activation with cerebral arterial contraction or relaxation are more effective in perinatal than in adult baboons.     

Anatomical variations of the arterial pattern in the right hemiliver

The arterial supply to the right hemiliver was studied in 80 liver casts. The arteries were divided into 10 groups according to their origin and branching pattern. The right hemiliver was supplied by one artery in 96% of cases and by two arteries in 4%. When there was only one artery it originated from the proper hepatic artery in 73/77 cases and from the superior mesenteric artery in 4/77 cases. The replacing right hepatic artery which originated from the superior mesenteric vessel supplied the whole right hemiliver in 5% of cases. The incomplete replacing right hepatic artery which supplied only a part of the right hemiliver was found in 4% of cases. The anterior section (segments 5 and 8) was supplied by one artery in 61%, by two arteries in 30% and by three arteries in 9% of cases. The posterior section (segments 6 and 7) was supplied by one artery in 66%, by two arteries in 31% and by three arteries in 3% of cases. Segments 5 and 7 were predominantly supplied by one artery, whereas segments 6 and 8 by two arteries.     

Characteristics of myogenic reactivity in isolated rat mesenteric veins

Mechanisms of mechanically induced venous tone and its interaction with the endothelium and key vasoactive neurohormones are not well established. We investigated the contribution of the endothelium, l-type voltage-operated calcium channels (L-VOCCs), and PKC and Rho kinase to myogenic reactivity in mesenteric vessels exposed to increasing transmural pressure. The interaction of myogenic reactivity with norepinephrine (NE) and endothelin-1 (ET-1) was also investigated. Pressure myography was used to study isolated, cannulated, third-order rat mesenteric small veins and arteries. NE and ET-1 concentration response curves were constructed at low, intermediate, and high transmural pressures. Myogenic reactivity was not altered by nitric oxide synthase inhibition with N(ω)-nitro-L-arginine (L-NNA; 100 μM) or endothelium removal in both vessels. L-VOCCs blockade (nifedipine, 1 μM) completely abolished arterial tone, while only partially reducing venous tone. PKC (chelerythrine, 2.5 μM) and Rho kinase (Y27632, 3 μM) inhibitors largely abolished venous and arterial myogenic reactivity. There was no significant difference in the sensitivity of NE or ET-1-induced contractions within vessels. However, veins were more sensitive to NE and ET-1 when compared with corresponding arteries at low, intermediate, and high transmural pressures, respectively. These results suggest that 1) myogenic factors are important contributors to net venous tone in mesenteric veins; 2) PKC and Rho activation are important in myogenic reactivity in both vessels, while l-VOCCs play a limited role in the veins vs. the arteries, and the endothelium does not appear to modulate myogenic reactivity in either vessel type; and 3) mesenteric veins maintain an enhanced sensitivity to NE and ET-1 compared with the arteries when studied under conditions of changing transmural distending pressure.     

A hemodynamic model representation of the dog lung

The published morphometric data from human, cat, and dog lungs suggest that the power-law relationships between the numbers (Na and Nv) and diameters (Da and Dv) of arteries and veins and between the lengths (La and Lv) and diameters of the arteries and veins could be used as scaling rules for assigning dimensions and numbers to the intrapulmonary vessels of the arterial and venous trees of the dog lung. These rules, along with the dimensions of the extrapulmonary arteries and capillary sheet and the distensibility coefficients of the vessels obtained from the literature, were used to construct a steady-state hemodynamic model of the dog lung vascular bed. The model can be characterized approximately by 15 orders of arteries with Na approximately 2.07 Da-2.58 and 13 orders of veins with Nv approximately 2.53 Dv-2.61. For the intrapulmonary vessels (orders 1-12), La approximately 4.85 Da1.01, and Lv approximately 6.02 Da1.07. The average ratio of the numbers of vessels in consecutive orders is approximately 3.2 for the arteries and veins. These arterial and venous trees are connected by the capillary sheet with an undistended thickness of approximately 3.5 microns and an area of 33 m2. The average distensibility (% increase in diameter over the undistended diameter/Torr increase in transmural pressure) for the model arteries and veins is approximately 2.4%/Torr, and the distensibility of the capillary sheet (% increase in thickness over the undistended thickness/Torr increase in transmural pressure) is approximately 3.6%/Torr. The calculated arterial-capillary-venous volumes and compliances of the model agree well with experimental estimates of these variables in dogs. In addition, the model appears consistent with certain aspects of the pressure-flow relationships measured in dog lungs. The model appears to be a useful summary of some of the available data on pulmonary morphometry and vessel properties. It is anticipated that the model will provide the basis for dynamic modeling of the dog lung in the future.     

Relaxing effect of atrial natriuretic factor on endothelin-precontracted vascular strips

Endothelin (ET), a peptide recently isolated from the supernatant of cultured porcine aortic endothelial cells, is a potent vasoconstrictor. On the other hand, atrial natriuretic factor (ANF) is a powerful vasorelaxant found in cardiocytes. Its effect was investigated in ET-precontracted rabbit vascular strips. ANF-induced a dose-dependent relaxation of maximally-precontracted mesenteric, renal and aortic strips. Mesenteric artery strips were more sensitive to ANF than either renal or aortic strips. The relaxant effect of ANF on ET-precontracted arteries was more potent than that of other vasorelaxant agents, such as isoproterenol and sodium nitroprusside. Renal and aortic arteries were more sensitive to the vasoconstrictor effect of ET than mesenteric strips. From these results, we conclude that ANF may play a role as a physiological antagonist of ET. The different sensitivity of vascular segments to ET could be due to varying vascular ET receptor densities.     

Pituitary adenylate cyclase activating peptide (PACAP) in guinea-pig lung: distribution and dilatory effects.

The lower airways of guinea-pigs were analyzed for pituitary adenylate cyclase activating peptide (PACAP) using immunocytochemistry. In the trachea a moderate supply of PACAP-immunoreactive nerve fibers occurred around smooth muscle bundles, glands and small blood vessels. In the lung, PACAP-immunoreactive nerve fibers were distributed around small glands and bronchi. A rich supply of PACAP immunoreactive nerve fibers was found around blood vessels in the lungs. PACAP-suppressed smooth muscle responses were analysed using isolated circular segments of trachea, pulmonary arteries and aorta of guinea-pigs. In both airways and arteries PACAP caused a concentration-dependent relaxation of precontracted segments. The maximal relaxation effects were more pronounced in the airways than in the arteries while the order of potency was aorta greater than pulmonary artery greater than trachea. The effect of PACAP was compared to those of acetylcholine (ACh) and vasoactive intestinal peptide (VIP). In the pulmonary artery the vasomotor responses expressed as maximal dilatation had the order: ACh greater than VIP = PACAP while the order of potency was PACAP = VIP greater than ACh. In the trachea, PACAP was slightly more potent than VIP. The relaxatory responses to PACAP in the trachea and the intrapulmonary arteries were unaffected by pretreatment with atropine, prazosin, yohimbine, propranolol, mepyramine, cimetidine and Spantide. Removal of the endothelium abolished PACAP-induced vascular relaxation. Conceivably, PACAP-containing nerve fibers play a role in the regulation of airway resistance and local blood flow.     

As human pial arteries (internal diameter 200-1000 microm) get smaller, their wall thickness and capacity to develop tension relative to their diameter increase.

Pial arteries play a key role in the regulation of human cerebral blood flow. However, many of the features and mechanisms that regulate the tone and diameters of these vessels cannot be studied in situ. One approach is to study in vitro segments of arteries obtained during neurosurgical procedures. The ratios of arterial media thickness to lumen diameter and of the capacity to develop wall force to lumen diameter have important functional consequences and are known to change in disease. Experiments were carried out on pial arteries from normotensive humans to determine the way in which these parameters vary with vessel size. Vessel dimensions--media thickness and lumen diameter were derived from fixed sections using quantitative morphometry. Wall force was measured using a resistance artery myograph. The ratio of media thickness to lumen diameter and of maximum tension developed to lumen diameter both increased as vessel diameter decreased. These ratios do not change over the age range of 15-75 years. These findings show that although in vivo intralumenal pressure falls as human pial arteries become smaller, their media thickness and capacity to develop tone increase.     

Evidence for alpha-1 adrenergic receptor regulation of atriopeptin release from the isolated rat heart

Atrial myocardium is the source of a recently described peptide hormone termed atriopeptin. Atriopeptin is thought to have a role in the regulation of systemic arterial pressure, fluid balance and plasma electrolyte homeostasis. Isolated rat hearts release atriopeptin into the coronary effluent, and we have found that this release is stimulated by the administration of norepinephrine, a compound with alpha and beta adrenergic properties. Infusion of the pure beta-receptor agonist, isoproterenol, failed to stimulate the release; however, the alpha-1 receptor agonist phenylephrine induced the release in a dose-dependent manner. The stimulation of atriopeptin release by norepinephrine and phenylephrine was inhibited by alpha-blockade with phentolamine. Administration of BHT-920, a selective alpha-2 agonist, had no effect on atriopeptin release. We conclude that atriopeptin secretion by the atrial myocyte is stimulated by activation of the alpha-1 adrenergic receptor. This finding suggests an involvement of the sympathetic nervous system in the physiologic regulation of the secretion of this hormone.     

Arterial T and Y grafts.

Presented is the use of an autogenous arterial T graft for the salvage of a thrombosed arterial end-to-side anastomosis. The T-graft concept also offers the possibility of replacing a segment of artery in patients with arterial vessel wall defects, stenosis, obliteration, or disease during free latissimus dorsi or scapular flap transfer. The arterial T graft is harvested from the axilla and consists of segments of the subscapular, circumflex scapular, and thoracodorsal arteries. The large diameter of these vessels offers a good match with the arteries of the lower leg and forearm. The arterial Y graft consists of the same arteries and is used as an interpositional graft to revascularize two distal vessels from one proximal vessel.