Constrictor reaction to transmural electric stimulation of the isolated femoral artery and its branches in chronic arterial hypotension

Chronic regional arterial hypotension in the hind limbs of rats was produced by narrowing of the abdominal aorta. 14-19 days later the femoral artery and its main branches were isolated and perfused in vitro with oxygenated Krebs' solution. It was shown that constrictor responses to transmural electrical stimulation decreased 14-30 days after the constriction of the aorta, however, 90 days after the operation the responses were identical to those in the control. Guanethidine (1.10(-5) mol/l) decreased significantly the responses to stimulation in all the cases, while phentolamine (3.5.10(-5) mol/l) inhibited completely those reactions. The constriction of femoral arteries in response to noradrenaline infusion was the same in control and hypotensive vessels.     

Vertebrate phylogeny of hydrogen sulfide vasoactivity

Hydrogen sulfide (H(2)S) is a recently identified endogenous vasodilator in mammals. In steelhead/rainbow trout (Oncorhynchus mykiss, Osteichthyes), H(2)S produces both dose-dependent dilation and a unique dose-dependent constriction. In this study, we examined H(2)S vasoactivity in all vertebrate classes to determine whether H(2)S is universally vasoactive and to identify phylogenetic and/or environmental trends. H(2)S was generated from NaHS and examined in unstimulated and precontracted systemic and, when applicable, pulmonary arteries (PA) from Pacific hagfish (Eptatretus stouti, Agnatha), sea lamprey (Petromyzon marinus, Agnatha), sandbar shark (Carcharhinus milberti, Chondrichthyes), marine toad (Bufo marinus, Amphibia), American alligator (Alligator mississippiensis, Reptilia), Pekin duck (Anas platyrhynchos domesticus, Aves), and white rat (Rattus rattus, Mammalia). In otherwise unstimulated vessels, NaHS produced 1) a dose-dependent relaxation in Pacific hagfish dorsal aorta; 2) a dose-dependent contraction in sea lamprey dorsal aorta, marine toad aorta, alligator aorta and PA, duck aorta, and rat thoracic aorta; 3) a threshold relaxation in shark ventral aorta, dorsal aorta, and afferent branchial artery; and 4) a multiphasic contraction-relaxation-contraction in the marine toad PA, duck PA, and rat PA. Precontraction of these vessels with another agonist did not affect the general pattern of NaHS vasoactivity with the exception of the rat aorta, where relaxation was now dominant. These results show that H(2)S is a phylogenetically ancient and versatile vasoregulatory molecule that appears to have been opportunistically engaged to suit both organ-specific and species-specific homeostatic requirements.     

The effects of inhibitors of Rho- and tyrosine c-Src-kinases on serotonin-induced constrictions of the aorta and mesenteric artery in rats

We found that the inhibitor of Rho-kinase fasudil selectively inhibited constriction of isolated rings of the aorta and mesenteric artery in rats in response to application of the agonists of 5HT2A-(DOI and TBC-2) and 5HT1A-receptors (8-OH-DPAT) and did not influence vasoconstriction induced by serotonin. We demonstrate for the first time that application of the agonists of 5HT2C-receptors (MK 212 and SCH 23390) did not influence the tone of “intact” vessels. The marked vasoconstrictory effect of the agonists of 5HT2C-receptors was observed in the vessels preconstricted due to angiotensin II or vasopressin. We found that the inhibitor of Rho-kinase did not influence negatively on MK 212 or SCH 23390-induced constriction of isolated rings of the aorta and mesenteric artery in rats. We suppose that, in the presence of fasudil, serotonin induces constriction of vessels through the interaction with 5HT2C-receptors and signal transduction from these receptors does not involve Rho-kinase activity. We found that fasudil attenuated vasoconstriction induced by norepinephrine and vasopressin by 40%. We demonstrated that tyrosine c-Src-kinase plays the most important role in signal transduction from 5HT-receptors because its effects are specific with relation to these receptors.     

The inhibitors of the 5HT-transporter fluoxetine and clomipramine attenuate serotonin-induced constriction of the aorta and the calcium signal in smooth muscle cells of the rat

We found that the inhibitors of the serotonin (5HT) transporter fluoxetine and clomipramine significantly inhibit 5HT-induced constriction of isolated rings of the aorta. The most prominent inhibitory effect was observed for clomipramine, which at a concentration of 2 μM, prevented aorta constriction in response to low and moderate doses of 5HT and multiply attenuated it in response to high doses (10 μM). The inhibitors of the 5HT-transporter attenuated the strength of norepinephrine-induced aorta constriction by 40–60% and eliminated long-term tonic constriction. Application of clomipramine or fluoxetine on the vessels preliminarily constricted by norepinephrine resulted in 100% relaxation, which was maintained in the presence of the NO-synthase inhibitor L-NAME. The inhibitors of the 5HT-transporter decreased but did not prevent 5HT-induced [Ca²⁺]_cyt increase in smooth muscle cells (SMCs) of the aorta even at high concentrations. Clomipramine and fluoxetine did not affect the vasopressin-induced [Ca²⁺]_cyt increase in SMCs and the strength of constriction of isolated aorta rings. We found that the sensitivity of the rat aorta to the vasoconstrictor effect of 5HT and the role of the 5HT-transporter in regulation of the vascular tone increased with aging.     

Individual and age-related differences in the anatomy of the main deferent lymphatic vessels of the human heart and their applied significance

One hundred human hearts of various age have been investigated. Structure, size of their main deferent lymphatic vessels are defined by the organ's form, sex and age of the persons. According to the position signs, extreme forms of their topography have been revealed. In the left--the course in the adventitia of the anterior wall of the pulmonary trunk and of the ascending aorta. In the left--the course in the adventitia of the right lateral wall of the ascending aorta and of the pulmonary trunk. The number of the extraorganic vessels, that bring lymph out of the heart, is from 1 up to 3. The anastomoses made between certain parts of the lymph nodes and the extraorganic lymphatic vessels in the transplanted and removed hearts are more economic.     

Absence of acid phosphatase activity in specific endothelial organelles

Summary Endothelial specific organelles in the aorta and in the small pulmonary blood vessels were investigated by electron microscopy with respect to their acid phosphatase activity. As controls, acid phosphatase reactions performed on liver and lung tissue showed, as expected, positive results. Since the endothelial specific organelles were in each case free of reaction product, it was concluded that they do not have a lysosomal function.     

Anatomic features of the base of hearts with a solitary ventricle

Twenty-eight preparations of hearts having three chambers with two atria have been investigated. The age of the deceased was from several hours up to 21 years. Absence of the interventricular septum results in a complex rearrangement of the vessels in the basis cordis. Only in three cases the aorta and the pulmonary trunk situated typically, in others there was a complete transposition. Since the only ventricle, as a rule, is accompanied with a presence of a small chamber--"emissary", the topography of the vessels is mainly determined by the latter. The "emissary" is situated either along the right or left contour of the base of the common ventricle, its dimensions are variable. When the "emissary" is situated along the anterior-right contour of the basis cordis, as a rule, the aorta takes origin from the latter, its bulb is situated ventrally, initial parts of the venous arteries are visible. The cuspides of the aortal valve sag into the "emissary" lumen. When the aorta is situated normally, it can get off the cavity of the common ventricle, or the "emissary". The state of the children is determined first of all by the character of the pulmonary circulation. If there is no stenosis in the pulmonary trunk and it takes its origin from the common ventricle, or from the "emissary" of a great size, the prognosis is more favourable. Cases of early death among the children are connected with small size of the "emissary" chamber and a small diameter of the pulmonary trunk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of the endothelium in the development of the contractile reactions of vascular smooth muscle during decreased oxygenation

Noradrenaline-preactivated vascular smooth muscles (VSM) of the rat thoracic aorta showed two-phase reactions in response to decreased oxygenation: significant relaxation was preceded by transient constriction. When the endothelium was removed only VSM relaxation phase was retained, with no constriction observed. The data obtained suggest an endothelium-dependent nature of VSM constriction reaction to hypoxia, in contrast to endothelium-independent VSM relaxation. Intracellular calcium is also assumed to play an essential role in the formation of endothelium-dependent constriction VSM reaction to hypoxia.     

A model for hypoxic constriction of the pulmonary circulation

The detailed anatomic and biodynamic data provided for the cat lung by Zhuang et al. (J. Appl. Physiol. 55: 1341-1348, 1983) allowed pressure-flow curves for the normal lung to be generated. This model has been modified to permit the stimulation of the pressure and flow distribution effects of hypoxic pulmonary vasoconstriction for a two-compartment lung and generalized to allow comparison with the experimental results from dogs (and probably other species). Hypoxic pulmonary vasoconstriction is simulated by reduction of the initial diameter of the smallest six orders of pulmonary arteries. Expressions are presented that relate the alveolar and mixed-venous O2 tensions to a graded constriction of these vessels. In addition, the diameter of the capillary sheet and the six small arteries is defined with a maximum diameter at a transmural pressure of 20 cmH2O. Pressure-flow curves are derived for any combination of alveolar and mixed-venous O2 tension, alveolar and pleural pressure, left atrial pressure, and hematocrit. The two-compartment model is solved by an iterative procedure to identify the distribution of the flow and the resulting pulmonary arterial pressure when the compartments differ by size, hypoxic constriction, or other imposed conditions. The results of the model are compared with those from a variety of experimental preparations. It is concluded that the model is useful for identifying the quantitative causes of changes in the response to hypoxic pulmonary vasoconstriction and for the exploration of the functional influence of mechanical properties of the vasculature.     

Role of neuronal nitric oxide synthase in regulation of vascular and ductus arteriosus tone in the ovine fetus

Nitric oxide (NO) is produced by NO synthase (NOS) and contributes to the regulation of vascular tone in the perinatal lung. Although the neuronal or type I NOS (NOS I) isoform has been identified in the fetal lung, it is not known whether NO produced by the NOS I isoform plays a role in fetal pulmonary vasoregulation. To study the potential contribution of NOS I in the regulation of basal fetal pulmonary vascular resistance (PVR), we studied the hemodynamic effects of a selective NOS I antagonist, 7-nitroindazole (7-NINA), and a nonselective NOS antagonist, N-nitro-L-arginine (L-NNA), in chronically prepared fetal lambs (mean age 128 +/- 3 days, term 147 days). Brief intrapulmonary infusions of 7-NINA (1 mg) increased basal PVR by 37% (P < 0.05). The maximum increase in PVR occurred within 20 min after infusion, and PVR remained elevated for up to 60 min. Treatment with 7-NINA also increased the pressure gradient between the pulmonary artery and aorta, suggesting constriction of the ductus arteriosus (DA). To test whether 7-NINA treatment selectively inhibits the NOS I isoform, we studied the effects of 7-NINA and L-NNA on acetylcholine-induced pulmonary vasodilation. The vasodilator response to acetylcholine remained intact after treatment with 7-NINA but was completely inhibited after L-NNA, suggesting minimal effects on endothelial or type III NOS after 7-NINA infusion. Western blot analysis detected NOS I protein in the fetal lung and great vessels including the DA. NOS I protein was detected in intact and endothelium-denuded vessels, suggesting that NOS I is present in the medial or adventitial layer. We conclude that 7-NINA, a selective NOS I antagonist, increases basal PVR, systemic arterial pressure, and DA tone in the late-gestation fetus and that NOS I protein is present in the fetal lung and great vessels. We speculate that NOS I may contribute to NO production in the regulation of basal vascular tone in the pulmonary and systemic circulations and the DA.     

Cyclooxygenase-derived products, rather than nitric oxide, are endothelium-derived relaxing factor(s) in the ventral aorta of carp (Cyprinus carpio)

In some fish blood vessels, the existence of a NO (nitric oxide) system has been reported. We examined the possibility that this NO system acts as an endothelium-derived relaxing factor (EDRF) in carp aorta using the carp aorta alone and in a combined carp-rat aorta donor-detector system. Use of the typical NO stimulating agent in mammal acetylcholine (ACh) only induced constriction of the carp aorta. This response was not modified by denudation or by NO synthesis inhibition with N-nitro-L-arginine methyl ester. Neither the indirect NO stimulating agents bradykinin and histamine nor the direct NO releasers sodium nitroprusside (SNP) and SIN-1 induced vasorelaxation. Both SNP and ACh elevated the cGMP concentration in rat aorta, but not in carp aorta. In the aorta combination set-up, where carp served as a NO donor and rat aorta served as a NO detector, no relaxation of the rat aorta was observed. The calcium ionophore A23187, a known EDRF producer in mammals, induced relaxation of carp aorta through an endothelium- and cyclooxygenase-dependent mechanism. These results indicate that carp aorta does not produce NO as an EDRF nor does it respond to exogenously supplied NO. The major EDRF in carp is apparently a product(s) of cyclooxygenase metabolism.     

Development of the neural apparatus of blood vessels in the common frog in ontogenesis

The neural apparatus of the aorta, abdominal vein, ischiatic, femoral, pulmonary and caudal vessels has been studied histochemically in tadpoles (the 30th-50th stages of development) and in 1-year-old animals. It has been stated for the first time that in the frog, a representative of the Amphibia class, like in mammals and birds, formation of the adrenergic apparatus in various vessels does not take place simultaneously. For instance, the first adrenergic fibers in the hind limb vessels appear much earlier than in other arteries and veins. The process of the adrenergic innervation development and its completion in vessels of various areas is taking its course differently. In the aorta and in the abdominal vein the formation of the adrenergic plexus develops as increasing density and amount of the mediator in the adrenergic fibers and is completed with maturation in an adult animal. In contrast to these vessels, maturation of the adrenergic apparatus in the hind limb arteries and veins takes place during a shorter interval and is completed at the end of metamorphosis AchE-containing fibers are revealed in tadpoles, as well as in a mature frog only in the aortal arc and in the pulmonary artery. In these vessels the development of cholinergic innervation leaves behind that of the adrenergic innervation, as it does in the vessels of Mammalia, and the human subject.     

An Operation Designed to Promote the Growth of New Coronary Arteries,Using a Detached Omental Graft: A Preliminary Report

The human greater omentum exhibits a marked affinity for inflamed surfaces, to which it supplies numerous blood vessels. To achieve myocardial revascularization by omental graft the root of the aorta, the epicardium over both ventricles and the serosal layer of the pericardium were removed in 17 animals. A piece of greater omentum was removed from the abdomen, unfolded and wrapped around the entire heart, and fixed by interrupted sutures to the base of the aorta. Myocardial ischemia was created at the time of operation by ameroid constriction of coronary arteries. Vessels, arteriolar or larger, were found to grow from the root of the aorta, the myocardium and the pericardium into the detached free omental graft, which apparently acted as a conveyer for new vessels, including new coronary arteries, to reach the myocardium.     

Role of veins in regulation of pulmonary circulation

Pulmonary veins have been seen primarily as conduit vessels; however, over the past two decades, a large amount of evidence has accumulated to indicate that pulmonary veins can exhibit substantial vasoactivity. In this review, the role of veins in regulation of the pulmonary circulation, particularly during the perinatal period and under certain pathophysiological conditions, is discussed. In the fetus, pulmonary veins contribute a significant fraction to total pulmonary vascular resistance. At birth, the veins as well as the arteries relax in response to endothelium-derived nitric oxide and dilator prostaglandins, thereby assisting in the fall in pulmonary vascular resistance. These effects are oxygen dependent and modulated by cGMP-dependent protein kinase. Under chronic hypoxic conditions, pulmonary veins undergo remodeling and demonstrate substantial constriction and hypertrophy. In a number of species, including the human, pulmonary veins are also the primary sites of action of certain vasoconstrictors such as endothelin and thromboxane. In various pathological conditions, there is an increased synthesis of these vasoactive agents that may lead to pulmonary venous constriction, increased microvascular pressures for fluid filtration, and formation of pulmonary edema. In conclusion, the significant role of veins in regulation of the pulmonary circulation needs to be appreciated to better prevent, diagnose, and treat lung disease.     

大鼠心力衰竭模型的构建与鉴定

目的比较主动脉弓缩窄和腹主动脉缩窄复制心力衰竭衰模型的异同,探索快速有效的心衰动物模型。方法将大鼠分为主动脉缩窄手术组,腹主动脉缩窄手术组和对照组（C组）。主动脉缩窄手术组实施颈部手术,在主动脉弓处缩窄动脉直径;腹主动脉缩窄手术组实施腹部手术,在腹主动脉处缩窄动脉直径;C组实施颈部手术但不实施动脉缩窄手术。各组实验动物均正常喂养4～6周后进行心脏的超声检测和心脏血流动力学检测。结果心脏超声结果显示：主动脉弓缩窄手术组左心室壁厚度和左心室腔内径在术后4周明显高于正常组;而腹主动脉缩窄手术组左心室壁厚度和左心室腔内径在术后4周较正常组没有明显增加。术后6周,腹主动脉缩窄手术组左心室壁厚度和左心室腔内径都明显增加,而主动脉弓缩窄手术组左心室壁厚度没有明显改变,左心室腔内经明显增加。血流动力学指标显示：主动脉弓缩窄手术组LVESP、LVEDP、LVDP、±dp/dtmax都明显低于腹主动脉缩窄手术组。结论主动脉弓缩窄手术复制心肌肥大导致心功能衰竭模型效果明显快于腹主动脉缩窄手术复制的心肌肥大导致心功能衰竭模型。     

Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo

Bandeiraea simplicifolia B4 isolectin (BSLB4) and polyclonal antisera against von Willebrand factor (VWF) were used to study the origin of endothelial cells and their organization into blood vessels in the postimplantation mouse embryo. Examination of BSLB4-stained whole mounted and sectioned embryos revealed intense staining of the endothelium, highlighting large vessels, capillaries, and many individual cells. Dorsal aorta formation was first obvious at E7 when many lectin-positive cells appeared in paraxial and lateral plate mesoderm. As development proceeded to E8, BSLB4-positive cells became organized into craniocaudal lines destined to become the aorta proper. At E9, BSLB4 stained all vessels of the embryo including the dorsal aorta, the intersomitic arteries, and the endocardium. VWF expression was not detected until E8 when BSLB4/VWF double-stained sections revealed the dorsal aortae as the first VWF-positive vessels, while other endothelium visible with BSLB4 remained negative for VWF immunostaining. By E12 many other vessels became VWF-positive, including the aortic arches, the intersomitic arteries, and the cardinal veins. However, many angioblasts and capillaries remained VWF-negative, reflecting the heterogeneous expression of VWF among endothelium that has been reported in adults of other species. The histochemical data reported here support the conclusions of earlier avian studies by showing distinct vascular patterns in the initial formation of vessels from isolated angioblasts (vasculogenesis), followed by the extension and organization of the initial vascular structures (angiogenesis). Moreover, our data suggest that the endothelium arises from distinct VWF-positive sources associated with the dorsal aorta, as well as VWF-negative sources associated with other vessels in the embryo.     

A theory for water and macromolecular transport in the pulmonary artery wall with a detailed comparison to the aorta

The pulmonary artery (PA) wall, which has much higher hydraulic conductivity and albumin void space and approximately one-sixth the normal transmural pressure of systemic arteries (e.g, aorta, carotid arteries), is rarely atherosclerotic, except under pulmonary hypertension. This study constructs a detailed, two-dimensional, wall-structure-based filtration and macromolecular transport model for the PA to investigate differences in prelesion transport processes between the disease-susceptible aorta and the relatively resistant PA. The PA and aorta models are similar in wall structure, but very different in parameter values, many of which have been measured (and therefore modified) since the original aorta model of Huang et al. (23). Both PA and aortic model simulations fit experimental data on transwall LDL concentration profiles and on the growth of isolated endothelial (horseradish peroxidase) tracer spots with circulation time very well. They reveal that lipid entering the aorta attains a much higher intima than media concentration but distributes better between these regions in the PA than aorta and that tracer in both regions contributes to observed tracer spots. Solutions show why both the overall transmural water flow and spot growth rates are similar in these vessels despite very different material transport parameters. Since early lipid accumulation occurs in the subendothelial intima and since (matrix binding) reaction kinetics depend on reactant concentrations, the lower intima lipid concentrations in the PA vs. aorta likely lead to slower accumulation of bound lipid in the PA. These findings may be relevant to understanding the different atherosusceptibilities of these vessels.     

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Pulmonary arteries (PA) are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca2+ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the alpha1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (< or =3 microM) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in alpha-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca2+ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca2+ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation.     

Expression of myogenic constrictor tone in the aorta of hypertensive rats

We investigated the effect of intraluminal pressure or stretch on the development of tone in the descending thoracic aorta from rats with aortic coarctation-induced hypertension of 7-14 days duration. Increments of pressure >100 mmHg decreased the diameter of thoracic aortas from hypertensive but not from normotensive rats. The pressure-induced constriction was not demonstrable in vessels superfused with calcium-free buffer. Stretched rings of aorta from hypertensive rats exhibited a calcium-dependent constrictor tone accompanied by elevated calcium influx that varied in relation to the degree of stretch. Blockers of L-type calcium channels and inhibitors of protein kinase C reduced both basal tone and calcium influx in aortic rings of hypertensive rats. Hence, the thoracic aorta of hypertensive rats expresses a pressure- and stretch-activated constrictor mechanism that relies on increased calcium influx through L-type calcium channels via a protein kinase C-regulated pathway. The expression of such a constrictor mechanism is suggestive of acquired myogenic behavior.     

Dilator actions of endothelin in coronary resistance vessels and the abdominal aorta of the guinea pig

Endothelin has been characterized as a potent constricting factor. The purpose of this study was to investigate possible dilator effects of this peptide and to examine whether dilator responses occur through an endothelium-mediated mechanism in guinea pig coronary resistance vessels and isolated aortic rings. Changes in perfusion pressure after bolus injections of endothelin were measured using a constant-flow modified Langendorff preparation with a transducer between the flow pump and the heart. An immediate fall in perfusion pressure, averaging 6 mmHg, was observed after injection of endothelin (10(-14)-10(-12) moles). This effect was maximal at 1 minute and tended to return toward baseline levels within 4 minutes. In response to endothelin (10(-9) M), isolated aortic rings relaxed 35% after being contracted with prostaglandin F2 alpha (10(-7) M). In both preparations, dilation was converted to constriction after endothelium damage by oxygen radicals or endothelium removal (mechanical rubbing). Dilator responses to endothelin were blocked by pretreatment for 30 minutes with indomethacin (14 microM) in the presence of an intact endothelium in coronary resistance vessels, whereas in the abdominal aorta they were not. We conclude that endothelin has significant dilator properties and that this effect is opposed by its constrictor action at higher doses. In addition, dilator responses to endothelin require an intact endothelium in both coronary vessels and abdominal aorta. Finally, endothelin-induced dilation in coronary resistance vessels appears to occur through a cyclooxygenase product-mediated mechanism.