Human pulmonary vessels obtained from necropsy produce less prostacyclin and thromboxane than fresh vessels obtained from operations.
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6-Ketoprostaglandin F1 alpha↗
Biomedical subjects
J A Bevan
Publications and source records attributed to J A Bevan.
A comparison of human pulmonary arterial and venous prostacyclin and thromboxane synthesis--effect of a thromboxane synthase inhibitor.
The amounts of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) produced by the endothelial surfaces of paired samples of human pulmonary arteries and veins, obtained from patients undergoing thoracic surgery, were measured. The amounts of 6-keto-PGF1 alpha and TxB2 produced by arteries compared with veins were not different. However, both arteries and veins produced more 6-keto-PGF1 alpha than TxB2, the ratio being approximately 7.5:1 for both. 6-keto-PGF1 alpha synthesis by arteries was significantly correlated with that produced by veins but the relative amounts of TxB2 were not correlated. 6-keto-PGF1 alpha synthesis was correlated with TxB2 synthesis for veins but not for arteries. 8 of the 12 arterial samples exhibited some degree of intimal fibrosis. Incubation with the thromboxane synthase inhibitor, dazoxiben , caused a significant inhibition of vascular TxB2 synthesis and a significant increase in 6-keto-PGF1 alpha synthesis. In 3 of the 5 cases the increase in 6-keto-PGF1 alpha was too large to be explained by the fall in TxB2.
6-Ketoprostaglandin F1 alpha↗
Perivascular nerves with immunoreactivity to vasoactive intestinal polypeptide in cephalic arteries of the cat: distribution, possible origins and functional implications.
The distribution of nerves containing vasoactive intestinal polypeptide(VIP)-immunoreactive material was examined in the cephalic arteries and cranial nerves of cats using an indirect immunofluorescence procedure on whole mounts. Perivascular VIP-immunoreactive nerves were widely distributed in arteries and arterioles supplying glands, muscles and mucous membranes of the face. Within the cerebral circulation, perivascular VIP-immunoreactive nerves were most abundant in the circle of Willis and the proximal portions of the major cerebral arteries and their proximal branches supplying the rostral brainstem and ventral areas of the cerebral cortex. Nerves containing VIP-immunoreactive material were absent from distal portions of arteries supplying the posterior brainstem, cerebellum and dorsal cerebral cortex. Cerebral perivascular VIP-immunoreactive nerves had extracerebral origins probably from VIP-immunoreactive perikarya within microganglia in the cavernous plexus and external rete. Extracerebral perivascular VIP-immunoreactive nerves probably arose from VIP-immunoreactive perikarya in microganglia associated with the tympanic plexus, chorda tympani, lingual nerve and Vidian nerve as well as from cells in the otic, sphenopalatine, submandibular and sublingual ganglia. Therefore, it seems likely that each major segment of the cephalic circulation is supplied by local VIP-immunoreactive neurons. If the VIP-immunoreactive nerves cause vasodilation, they are well placed to allow redistribution of arterial blood flow within the head. During heat stress, neurogenic vasodilation of the appropriate beds would permit efficient cooling of cerebral blood, particularly that supplying the rostral brainstem and surrounding areas of the cerebral cortex.
Acetylcholine↗
Retroglenoid venoconstriction and its influence on canine intracranial venous pressures.
Using standard in vitro techniques, we found that the canine retroglenoid vein, a vessel that drains a significant fraction of canine cerebral venous effluent, demonstrated the following: an average wall thickness of approximately 240 microns; a norepinephrine (NE) content of approximately 3 micrograms/g tissue; a NE uptake capacity (uptake 1) of approximately 8 nmol/g tissue; an ED50 for NE of 1.9 X 10(-8) M; and a phentolamine-sensitive constriction during electric transmural stimulation that had a median effective frequency of approximately 3 Hz and a maximum response that was approximately 84% of the maximum response to exogenous NE. In a separate series of in vivo experiments conducted in six alpha-chloralose-anesthetized dogs, we found that electrical stimulation of the left superior cervical ganglion produced a phentolamine-sensitive, frequency-dependent increase in cerebral venous pressure (CVP) of up to 19 mm Hg when all cerebral venous effluent was diverted through the left retroglenoid vein. Taken together, our findings suggest that the canine retroglenoid vein undergoes a marked vasoconstriction during physiological frequencies of electric sympathetic nerve stimulation in vivo. Although our data further suggest that the retroglenoid is not a dominant influence on CVP in the intact dog, they do encourage a cautious interpretation of cerebral venous outflow data obtained with techniques in which cerebral effluent is drained primarily by extracranial veins.
Animals↗
Ultrastructure of the innervation of the cat lingual artery in relation to noradrenergic vasoconstriction, and to neurogenic vasodilation produced by cholinergic and nonadrenergic, noncholinergic mechanisms.
The lingual artery is one of several arteries in the head of the cat which have been found to contain both a noradrenergic neural vasoconstrictor mechanism, and neural vasodilator mechanisms which appear to utilize acetylcholine as well as a second neurotransmitter (possibly a peptide). In this study, after fixation of lingual arteries by the chromaffin method, both adrenergic and noradrenergic nerves were found at the adventitiomedial border and within the outer third of the tunica media. All of the nonadrenergic nerves had a similar structural appearance, containing mostly small clear vesicles. There may be a single population of dilator nerves containing both acetylcholine and a second transmitter, or there may be two populations of dilator nerves with the same structure, each containing a different transmitter.
Animals↗
Presynaptic alpha-receptor control of adrenergic transmitter release in blood vessels.
The presynaptic alpha-adrenergic receptor control of transmitter release in vascular tissues is discussed. A model of adrenergic innervation of the vascular bed is proposed based on ultrastructural and histochemical evidence. Evidence is presented to support the concept of intermittent or periodic release of norepinephrine (NE) from the varicosity. Intermittency combined with a mechanism such as presynaptic control to ensure spatial distribution of release sites, along with a slow effector response and recovery, results in a smooth, generalized change in tone and an overall economy of transmitter. The effective concentration of NE around the presynaptic membrane is maintained for considerably less than 0.1 s. It is argued that the transient presence of transmitter in the synapse combined with intermittency of release does not favor accumulation of transmitter at the cleft at physiological frequencies or desensitization of presynaptic receptors. In addition, intermittency provides an explanation for why exogenous NE is more effective presynaptically in influencing release than endogenous NE. The importance of cleft width in presynaptic control of transmitter release, the possible complications caused by facilitation, and resolution of some apparent problems with the presynaptic hypothesis are also discussed.
Action Potentials↗
Patterns of alpha-adrenoceptor regulation of the vasculature.
There are patterns in the distribution of the characteristics of vascular alpha-adrenoceptors. Sudden changes in their mechanism occur at particularly sites along the main branches of the aorta; in some regional vascular beds, but not others, there is a progressive reduction in the response that can be elicited through the alpha-adrenoceptor; in smaller blood vessels, alpha- and beta-adrenoceptors may be spatially separated in the vessel wall; in most blood vessels, the inner smooth muscle is more sensitive to alpha-agonists and more dependent on sequestered calcium than the outer. There is little support for a significant physiological role of the proposed gamma-receptor.
Animals↗
Vasoactive intestinal polypeptide and acetylcholine are responsible for neurovasodilation in the head of the cat.
There is reason to believe that the dilator innervation to blood vessels of many of the tissues of the head may be part of a common outflow from the central nervous system. Part of the effect of its activation is due to the release of acetylcholine and evidence is presented that, in addition, vasoactive intestinal polypeptide (VIP) release also plays a role. The non-cholinergic part of the dilator response to nerve activity can in a series of blood vessels be correlated with the level of VIP in their wall and is selectively reduced by VIP antiserum. In addition, VIP has suitable characteristics as a vasodilator. Whereas substance P which is present in the walls of many arteries of the head, does not qualify as a putative dilator transmitter. Despite the fact that the physiological role of dilator innervation to the circulation as a whole is not understood, the powerful consequences of the activation of the system in particular blood vessels suggests that this innervation should be seriously considered when studying the regulation of peripheral resistance.
Acetylcholine↗
The human adrenergic neurovascular mechanism.
Although evidence is limited and derived from many studies with many different objectives on a variety of blood vessels under varying experimental conditions, it appears that the human adrenergic vascular neuroeffector mechanism is qualitatively similar to that defined in studies on animals. The characteristics of the alpha-adrenoceptor based upon pA2 measurements and other pharmacological characteristics show it to be similar to adrenoreceptors defined in animals. The sensitivity of vascular smooth muscle to norepinephrine is of the same order throughout the human vasculature and is similar to that seen in most animal vessels. In most blood vessels the alpha-adrenoreceptor is the dominant type. By contrast the beta-adrenoceptor component is usually small with a high threshold except in the coronary artery and facial vein. Sympathetic frequency-response relationships of both arteries and veins are similar to those from animal studies. The human alpha-adrenoceptor is coupled both to sequestered calcium sites and slow calcium channels, and these two mechanisms are responsible for the biphasic response of human blood vessels to norepinephrine. The slow calcium channel but not the sequestered calcium system is sensitive to calcium antagonists. There is evidence that the human adrenergic mechanism is altered in disease.
Arteriosclerosis↗
Electrical stimulation causes endothelium-dependent relaxation in lung vessels.
Ring segments of blood vessels were isolated from the lungs of rabbits, cats, and monkeys. After constriction with norepinephrine, electrical field stimulation caused smooth muscle relaxation in these segments. Mechanical removal of the endothelial layer, verified by scanning electron microscopy, abolished or greatly attenuated the relaxation. The response could be restored in part by apposing the endothelial surface of another vessel segment and the denuded inner surface of the constricted vessel segment. Incubation with tetrodotoxin, procaine hydrochloride, guanethidine, propranolol, atropine, metiamide, indomethacin, quinacrine hydrochloride, 5,8,11,14-eicosatetraynoic acid, aminophylline, and verapamil failed to block or enhance the relaxation response to field stimulation. We conclude that the vascular endothelium in the larger pulmonary arteries and veins studied contains a diffusible substance that inhibits smooth muscle contraction. Its release by electrical field stimulation in vitro does not involve classic neuronal transmitter release or metabolism of arachidonic acid by cyclooxygenase or lipooxygenase.
Acetylcholine↗
Adrenergic control in three artery segments of diminishing diameter in rabbit ear.
The adrenergic neuroeffector mechanism has been assessed in three different-sized vessels of the rabbit ear, i.e., the central ear artery (CEA), which has an unstretched lumen diameter (ULD) of approximately 300 micron; a main side branch (MSB) that comes off the CEA immediately distal to the crossover position of the central vein (ULD approx 150 micron); and a terminal branch (TB) that originates from the MSB (ULD approximately 75 micron). The vessels receive adrenergic innervation limited to the adventitia as assessed by fluorescence histochemistry. Density of innervation, as indexed by neuronal uptake of tritiated norepinephrine (NE) and NE content expressed in terms of surface area of the vascular segment, appears greater in the larger vessel than in the small vessels. The neurogenic contractile response of isolated segments in relation to the maximum response to iota-NE was significantly greater in CEA than in the smaller vessels; this paralleled the neuronal density. Phentolamine (10(-6) M) blocked neurally evoked contractions of ear vessels at 2 Hz and depressed the contraction at least 90% at 4 and 8 Hz. All arterial segments constricted in response to histamine and NE with equal maximal effects. Sensitivity to NE appeared equal, whereas that to histamine appeared greater in the smaller vessels. Only the two smaller vessels possessed intrinsic tone. On the basis of the substantial innervation and neurogenic response of the vessels studied, (substantive) sympathetic control of vascular tone occurs in the three different-sized vessels of the rabbit ear, a fact that may be related to the temperature regulation role of that vascular bed.
Animals↗
Medial morphometry and mechanics of sequential rabbit ear arteries and myograph ring segments.
The medial structure of three different branching orders of arteries in the rabbit ear was studied to assess the possible significance with regard to mechanical behavior determined with the in vitro myograph. The central ear artery, its main side branch, and a terminal branch were fixed while dilated in situ at 100 mmHg; this resulted in internal diameters of 960, 456, and 251 micron, respectively. The average ratio of medial thickness to internal diameter was 0.0293 for arteries in situ and 0.0487 for arterial rings in vitro. Measurements undertaken for the determination of smooth muscle (SM) stress included the percentage of SM in the media (74%) and the pitch of SM (0.89 degrees). These parameters were not significantly different in the three various-sized arteries or for the two myographs. Stereological estimates of SM cell volume, length, and diameter were based on counts of SM nuclei and their length. In evaluating the ring preparation of the vessel myographs, the damage due to the wires (20%) and cut edges (6.4%) was considered. The maximum active SM stress was approximately the same in the different-sized vessels with an average value of 3.14 X 10(5) N/m2. Since this stress is comparable to measurements made by others on different mechanical apparatus and consistent for the three arterial orders, these in vitro myographs should allow for valid comparison of arterial mechanical properties over the size range studied.
Animals↗
Effect of contraction on the subsequent responsiveness and maximum contractility of the rabbit ear artery and saphenous vein in vitro.
The purpose of this study was to investigate the effect of prior agonist-induced contraction of vascular smooth muscle on its subsequent responsiveness and maximum contractility. Repeated exposure of the rabbit ear artery to equieffective histamine (Hist) or KCl concentrations increased subsequent norepinephrine (NE) responsiveness and maximum contractility in comparison to rested controls. Tissues exposed in a similar manner to an equieffective serotonin concentration responded to NE more than did controls, but less than Hist- and KCl-pretreated tissues. Prior exposure to NE or KCl increased Hist responsiveness and maximum contractility. However, NE pretreatment did not increase serotonin or KCl responsiveness. The increased responsiveness and maximum contractility lasted for at least 90 and 390 min., respectively. When ear arteries were exposed to agonists in the presence of NaNO2 or papaverine the increase in responsiveness was either reduced or absent. Everted arteries repeatedly exposed to Hist demonstrated an increased tonic phase contraction to NE; there was no change in the initial transient phase of contraction. Exposure of the saphenous vein to Hist oe KCl had no effect on subsequent NE responsiveness; however, maximum contractility was increased. The present results suggest that (1) contraction brought about by agonist drugs can result in two separate phenomena -- increased responsiveness and increased maximum contractility; (2) the increased responsiveness may mask underlying alpha-adrenoceptor desensitization which may be agonist specific; (3) an event following agonist-receptor binding is responsible for increased responsiveness and increased maximum contractility; (4) the mechanism for increased responsiveness may be due to an increased coupling between receptor activation and membrane permeability to calcium; (5) agonist contraction in the saphenous vein and ear artery may be regulated by different mechanisms.
Animals↗
Importance of 'cut-end' effects in in vitro artery segments.
In order to investigate the consequence of cutting a vascular segment upon its performance in vitro, the contractions of a 4-mm-long segment of ear artery to neurogenic and exogenous norepinephrine (NE) were compared to those of a similar segment cut in half. The active wall tension developed in response to exogenous NE was significantly greater in the 4-mm one-ring segment length (8.50 +/- 0.56 mN/mm) than in the two-ring 2-mm segment lengths (6.64 +/- 0.38 mN/mm) while the EC50 values were the same. The maximum tone (tension) developed at a given frequency of transmural electrical stimulation, expressed as a percentage of maximum tone developed to exogenous NE, was significantly greater (285%) in the one-ring 4-mm segment length than in the two-ring 2-mm segment lengths at the lowest frequency tested (1 Hz) while the tone was approximately equivalent at the higher frequencies (2, 4, 8 Hz). On histological examination, the internal diameter of the artery at the cut ends was less than the remainder of the segment and corresponded with a terminal zone in which the smooth muscle cells, both nuclei and cytoplasm were more deeply stained by hematoxylin and eosin. The transverse diameters of the nuclei and the cells in the end region were reduced so that the muscle cells appeared compressed. Segment 'cut-end' effects would be expected to be relatively more important in shorter ring segment lengths of vessel compared to longer segments.
Animals↗
Facial vein of the rabbit. Intracellularly recorded hyperpolarization of smooth muscle cells induced by beta-adrenergic receptor stimulation.
A segment of the facial vein of the rabbit gains myogenic tone when placed under tension in a tissue bath (Winquist and Bevan, 1977); low frequency electrical stimulation of intramural nerves, or application of norepinephrine or isoproterenol produces relaxation, which is blocked by propranolol (1.0 microM). We measured membrane potential of single smooth muscle cells with microelectrodes during this beta-adrenergic receptor-mediated relaxation of the vein segment. Hyperpolarization (up to 30 mV) invariably accompanied relaxation. Average maximum resting potential recorded in normal Krebs solution was -46.8 +/- 3.6 mV (mean +/- SE); this increased to -70.8 +/- 3.0 mV when high concentrations (greater than 10 nM) of isoproterenol were added to the bath. Tone and membrane potential were very sensitive to intramural nerve stimulation. At 3-4 Hz, relaxation was about half maximal and hyperpolarization was 6-9 mV. The maximum hyperpolarization to nerve stimulation was 20-30 mV, about the same magnitude as that produced by isoproterenol. Hyperpolarization clearly preceded relaxation by about 0.2 second. The magnitude of hyperpolarization in facial vein is much larger (2-10 times or more) than that recorded in other tissues during inhibition produced by stimulation of beta-adrenergic receptors. The large hyperpolarization may augment the effectiveness of inhibition (by curtailing potential dependent influx of Ca++o, for example) in this tissue compared to that in other tissues in which hyperpolarization is slight or absent. The ionic mechanism underlying hyperpolarization resulting from stimulation of beta-adrenergic receptors remains unclear.
Animals↗
Diltiazem selectively inhibits cerebrovascular extrinsic but not intrinsic myogenic tone. A review.
The tone of blood vessels resulting from extrinsic influences is dependent on activator calcium derived from sequestered cellular and also extracellular sources. Experiments on rabbit blood vessels in vitro show that--in comparison to systemic vessels--the contractions of cerebral arteries are proportionately more dependent on extracellular calcium and have sequestered calcium sources that are more easily depleted. Both these observations suggest that activator calcium mechanisms differ at least quantitatively in cerebral compared to noncerebral vessels. Diltiazem antagonizes agonist-induced tone in cerebral arteries at a lower concentration than is required in systemic arteries and veins. For example, the concentration of diltiazem to halve the response of the rabbit basilar artery to norepinephrine (ED50) is 1 X 10(-8) M, whereas those for the ear and mesenteric arteries and the saphenous vein are 10.4, 2.0, and 1.8 X 10(-7) M, respectively. A similar selectivity has been found to K+ and serotonin-induced contractions. It has been argued that the neuroeffector mechanism in the portal vein reflects that in systemic resistance vessels. The drug is effective against the spontaneous rhythmic activity of the longitudinal muscle of the vein, reducing it to half at 1.5 X 10(-7) M. Diltiazem is relatively ineffective in antagonizing intrinsic smooth muscle tone, both cerebral (basilar) and extracerebral (facial vein) requiring ED50 values of 4 and 5 X 10(-4) M, respectively. In summary, our in vitro experiments on rabbit tissue show that diltiazem selectively antagonizes cerebrovascular extrinsic but not intrinsic tone.
Animals↗
Selective action of diltiazem on cerebral vascular smooth muscle in the rabbit: antagonism of extrinsic but not intrinsic maintained tone.
Diltiazem selectively reduces the second equilibrium phase of contraction of several arteries and veins in the rabbit to a number of agonists, including norepinephrine, serotonin, histamine and potassium. Its effect is consistent with blockage of the entry of activator calcium from the extracellular space into the vascular smooth muscle cell. It has a preferential action on responses of the basilar artery in comparison with those of the ear and mesenteric arteries and saphenous vein. Although the spontaneously developing, maintained intrinsic tone of the basilar artery and facial vein are very resistant to diltiazem, the spontaneous rhythmic activity of the portal vein is sensitive to its antagonistic action. Findings reported here are consistent with the possibility that diltiazem preferentially blocks receptor-operated and potential-sensitive slow calcium channels of the cerebral artery compared with other systemic vessels tested but has little effect on the mechanisms responsible for maintained intrinsic tone development.
Animals↗
Distribution of choline acetyltransferase in cerebral and extracerebral cranial arteries of the cat. Its relationship to neurogenic atropine-sensitive dilation.
Choline-acetyltransferase (ChAT) activity was surveyed in segments of cranial arteries--both cerebral and extracerebral--from the cat. High levels were found in pial arteries, both cerebral and cerebellar, and in the arteries to salivary glands, tongue, and nose. Intermediate levels were found in the external and internal maxillary arteries and many of their branches. Enzyme levels in the arteries supplying the head--common carotid, vertebral, and in several systemic arteries and veins and also the lingual vein--were probably not significant. Only those vessels that have higher ChAT contents show capacity for neurogenic vasodilation. The dilation of segments of a number of these arteries, the basilar, middle cerebral, lingual, and internal maxillary, is reduced significantly by atropine (5 X 10(-7) M). ChAT activity did not correlate with vessel norepinephrine content. The data may be interpreted as defining a functional vasodilator system to the head encompassing both cerebral and extracerebral arteries that depends in part on a functional cholinergic link involving a muscarinic receptor. It is separate from the adrenergic outflow. The tissues supplied by vasculature receiving this type of innervation are of ectodermal origin.
Animals↗