摘要:

&NA;The release of acetylcholine from autonomic nerves in those tissues that receive a cholinergic innervation is widely believed to dilate blood vessels. Exogenously administered acetylcholine in vivo does dilate vascular beds and produce hypotension; however, this latter effect is indirect and probably the result of liberation of endothelium‐derived relaxing factor (EDRF) from endothelial cells. Some blood vessels contain a substantial population of medial constrictor receptors for acetylcholine, and the implications of this presence for vascular control systems has been largely ignored, although it needs to be considered. A survey of the evolution of vasomotor control systems indicates that acetylcholine serves principally as an excitatory transmitter to blood vessels. Neurally mediated cholinergic constriction and not dilation is found in fish, amphibians, reptiles, and birds, with responses initiated by medial muscarinic receptors. Acetylcholine constricts many vascular preparations from these lower animals, but some vessels relax, reflecting the emergence of an EDRF responsive to acetylcholine. An examination of cholinergic responses in mammalian vessels reveals that cholinergic (neurogenic) dilation is limited to a very few vascular beds and to only a few species. Both experimental evidence and evolutionary considerations support the likelihood that cholinergic (neural) constriction operates in some vascular regions in mammals and, in particular, in the coronary circulation of some species, including humans. In fact, constriction, and not dilation, may be the dominant vascular response to activation of the cholinergic axis in most mammals, including humans. The complications and contradictions introduced by the simultaneous presence of both EDRF and a cholinergic constrictor innervation involving medial muscarinic receptors are discussed. A variety of evidence is also presented that implicates cholinergic constriction in at least some instances of coronary artery spasm and sudden death. (Circulation Research1989;65:237‐257)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Isoproterenol treatment leads to endomyocardial fibrosis with muscle fibers encircled by fibrillar collagen. This study was undertaken in the rat to determine if muscle encased in collagen would subsequently become either necrotic or atrophic. For this purpose, we monitored the fibrillar nature of myocardial collagen, its alignment with muscle, and the morphology of the endomyocardium, together with the response in diastolic and systolic myocardial stiffness, immediately on completion (10 days) and 30 days after a course of subcutaneous isoproterenol (500 &mgr;g/kg/day). We found 1) left ventricular hypertrophy at 10 and 30 days with an increase in collagen volume fraction (p<0.01) that consisted of a meshwork of thick and thin collagen fibers that encircled endomyocardial muscle, 2) a variable reduction in endocardial muscle fiber diameter at 30 days with the greatest thinning seen in muscle encircled by fibrous tissue, and 3) an elevation (p<0.01) in the slope of the diastolic stress‐strain relation at 10 and 30 days. The developed systolic stress‐strain relation, which was elevated at 10 days (p<0.01), declined (p<0.05) with the reduction in endomyocardial muscle mass. Thus, endomyocardial muscle, encircled by fibrillar collagen, will atrophy over time, and this leads to a reduction in active stiffness. These findings may, in part, explain why progressive ventricular dysfunction accompanies chronic myocardial disease with endomyocardial fibrosis. (Circulation Research1989;65:258‐264)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The vasoconstrictor responses of isolated rat portal vein and aorta to synthetically prepared endothelin are investigated. Both preparations respond to 10−9M levels of the peptide although the aortic response is more sustained than that of the portal vein. Endothelin‐evoked contractions, unlike those evoked by scorpion &agr;‐toxins (which are homologous to endothelin) or by veratridine, are insensitive to tetrodotoxin or to the removal of sodium ions from the tissue‐bathing medium. Contractile responses to endothelin may still be observed in high‐potassium depolarizing medium and are not dependent on the presence of extracellular chloride; however, the responses are dependent on the presence of extracellular calcium and are blocked by nitrendipine, nifedipine, or nickel. Endothelin‐evoked uptake of45Ca into aortic tissue is also independent of extracellular sodium or potassium and is blocked by nifedipine. These data strongly suggest that endothelin acts at a site closely coupled to the calcium channel and that depolarization by sodium influx through voltage‐dependent channels is not involved in endothelin‐induced vasoconstriction. (Circulation Research1989;65:265‐271)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;To assess whether coronary spasm affects the progression of atherosclerosis and results in evolution of myocardial infarction, the role of coronary spasm on the fine structure of conduit coronary arteries was studied morphologically. Göttingen miniature pigs were fed a semisynthetic diet containing 2% cholesterol and 1.1% sodium cholate. One month after being on this diet, the pigs were anesthetized and the endothelium of a branch of the left coronary artery was denuded using a balloon catheter. X‐ray irradiation in a dose of 1,500 rad was given twice selectively to the area denuded, after 4 and 5 months of cholesterol feeding. Five months after endothelial denudation, transient (group A) and repetitive episodes (group B) of coronary spasm were provoked by single and periodic (five times every 5 minutes) intracoronary injections of serotonin (10 &mgr;g/kg/injection), respectively. The extent of spasm by serotonin at the previously denuded site was 84±4% (n=4) and 90±5% (n=6) narrowing in groups A and B (p=NS between groups), respectively. Forty minutes after the final administration of serotonin, the left coronary artery was relaxed by nitroglycerin, and the heart was isolated and perfuse‐fixed under physiological pressure. Intramural hemorrhage was noted at the spastic site in six pigs of group B but not in group A. The average percent luminal narrowing, on cross sections at the spastic site in group B, was significantly greater than in group A (56±7% vs. 23±5%,p<0.01). Scanning electron micrographs revealed that the endothelial lining was intact at the nonspastic site in both groups. In addition to the appearance of intercellular bridges at the spastic site in both groups, squeezing of endothelial cells and adhesion of white blood cells were present at the spastic site exclusively in group B. These findings are consistent with the hypothesis that repetitive spasm may have an important role in the progression of atherosclerosis and/or myocardial infarction. (Circulation Research1989;65:272‐282)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;We investigated vasoactive intestinal peptide (VIP)‐receptor pharmacology in failing and nonfailing human ventricular myocardium by examining [125I]VIP binding in membrane fractions of left ventricle and inotropic effects of VIP in isolated right ventricular trabeculae mounted in tissue baths. [125I]VIP binding demonstrated upwardly concave, curvilinear Scatchard plots consistent with two classes of binding sites. Only the high‐affinity (dissociation constant [Kd] 400‐800 pM) site could be regulated by guanine nucleotides. Compared with nonfailing heart, membranes derived from failing heart exhibited a twofold reduction in theKdof the high‐affinity VIP binding site, whereas the receptor density (Bmax) was decreased by 62%. In concordance with this decreased receptor density and increased affinity, the maximal contractile response of right ventricular trabeculae from failing right ventricles was decreased by 61%, and the dose‐response curve to VIP was left‐shifted approximately threefold. We conclude that the VIP receptor in failing human ventricular myocardium exhibits novel regulatory behavior consisting of increased receptor affinity and decreased receptor density. (Circulation Research1989;65:283‐294)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The electrophysiology of antidromic reentry, a less common phenomenon than orthodromic reentry, remains a poorly understood aspect of the Wolff‐Parkinson‐White (WPW) syndrome. We used a pacing model of ventricular preexcitation in patients without WPW, so that electrophysiological events in the normal pathway during atrial extrastimulation (A1‐A2technique) could be precisely delineated without the obscuring effect of an actual accessory pathway. Ventricular preexcitation was simulated by an A1‐V1sequential basic drive with A2‐V2extrastimulation at progressively shorter A1‐A2(equal to V1‐V2) coupling intervals. At each coupling interval tested within the zone of atrioventricular (A‐V) nodal effective refractory period (since anterograde block of A2was considered mandatory for manifestation of antidromic reentry), responses were assessed after A2alone (method I), V2alone (method II), and A2plus V2(method III, the complete preexcitation model). The entire pacing protocol was performed at two A‐V intervals, short (50 msec) and long (150‐180 msec), thereby simulating different proximities between the A pacing site and “accessory pathway” location. Of 47 consecutive unmedicated patients screened for the study protocol, 38 failed to meet minimal prerequisites for possible initiation of antidromic reentry because of failure in 18 (38% of total) to achieve anterograde A‐V nodal block of A2, even though 1:1 ventriculoatrial conduction to cycle lengths less than or equal to 500 msec (≤400 msec in 12) was present; and poor or absent ventriculoatrial conduction in the others. The nine remaining candidates underwent the full pacing protocol. Antidromic reentry (retrograde atrial response following V2in method III) was observed in only two cases (4% of total), and both were associated with retrograde His‐Purkinje system delays (documented by method II) occurring in tandem with a long A‐V interval, thereby allowing for completion of retrograde A‐V nodal recovery after penetration by A2. Indeed, such a prolonged recovery time prevented initiation of antidromic reentry in six of the nine patients (proven by intact ventriculoatrial conduction in method II). Retrograde A‐V nodal block of V2, independent of A2, prevented an antidromic echo in one case. Findings in our model help to clarify the various factors, including specific anterograde and retrograde A‐V nodal properties; anatomic relation between the accessory and normal pathways; and the retrograde His‐Purkinje system delays, that must prevail in a concerted fashion to permit the initiation of antidromic reentry during the A1‐A2technique in patients with the WPW syndrome. (Circulation Research1989;65:295‐306)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Changes in right ventricular systolic function directly influence left ventricular systolic function. Most of our knowledge of this systolic direct ventricular interaction comes from studies of isolated hearts, which suggest that changes in right ventricular size only affect left ventricular systolic function at low pressures and volumes. However, almost nothing is known about systolic direct ventricular interaction in a heart functioning in situ as a part of the intact circulation. We used sudden constriction of the pulmonary artery to assess the immediate effect of a change in right ventricular pressure and contraction pattern on left ventricular contraction and relaxation on the beat following the pulmonary artery constriction in anesthetized open‐chest dogs. By focusing on this first beat, we were able to avoid the confounding effect of series ventricular interaction, which changes left ventricular filling and, thus, indirectly influences left ventricular function. At baseline left ventricular end‐diastolic pressure of 9.6±2.1 mm Hg (mean±SD), sudden pulmonary artery constriction increased left ventricular peak systolic pressure by 3±2 mm Hg (2% change), left ventricular stroke volume by 2±2 ml (8% change), and monoexponential time constant of left ventricular pressure fall during relaxation by 9±6 msec (22% change). This increased left ventricular relaxation time constant was associated with altered regional segment length changes in the posterior and anterior left ventricular free walls during relaxation. We conclude that systolic direct ventricular interaction affects left ventricular systolic function and relaxation under normal conditions in the intact circulation. (Circulation Research1989;65:307‐315)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The responses of cerebral arteries to catecholamines and sympathetic nerve stimulation show wide variation between animal species. We examined the catecholaminergic histofluorescence and the contractile responses elicited by transmural electrical field stimulation and norepinephrine (NE) in proximal segments of human middle cerebral artery (MCA) obtained during autopsy. Twenty‐four percent of the specimens were obtained within 2 hours and 76% within 4 hours of death. A moderately dense catecholaminergic histofluorescence was seen in all segments of human MCA using the glyoxylic acid technique, counterstained with pontamine sky blue. However, only seven of 35 (20%) MCA segments tested showed tetrodotoxin‐blocked transmural electrical field stimulation contractions, and all of these were harvested within 4 hours of death. The responses were mostly seen in the most proximal MCA segments and, at 32 Hz, only achieved 6±1% of the maximal tissue contraction. NE caused two distinct responses in human MCA segments. At low concentrations, it acts via an &agr;‐like adrenoreceptor to cause contractions 20±3% of the maximal tissue response. The NE ED50s for the three successive segments were not different from each other; the value for the most‐proximal segment was 7.9±0.2×10−7M. At concentrations above 10−5M, this catecholamine acts on low‐affinity sites resistant to &agr;‐adrenergic antagonists causing contractions that at 10−3M reach 52±5% of the maximal tissue response. Our results suggest that it is important when studying human blood vessels to harvest them as soon as possible after death, that the smooth muscle response to sympathetic activation is small, frequently absent, and that the postsynaptic sympathetic mechanism includes not only &agr;‐adrenoceptors but low‐affinity sites as well. (Circulation Research1989;65:316‐324)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;&bgr;‐Adrenergic stimulation induced delayed afterdepolarizations and triggered activity in atrial fibers of adult but not young canine coronary sinus. However, sensitivity to &bgr;‐adrenergic agonists with respect to maximum diastolic potential was identical at both ages, and delayed afterdepolarizations and triggered activity did occur in response to ouabain. Age‐dependent lengthening of the action potential duration and plateau also were seen and were greater in the adult than the young. &bgr;‐Adrenergic receptor density and affinity and the stimulatory guanine nucleotide regulatory protein (Gs) were similar in adult and young tissues. In contrast, the inhibitory guanine nucleotide regulatory protein (Gi) was 2.5‐fold greater in adult (15 fmol/mg) than in young (6.0 fmol/mg) tissues. Basal‐ and forskolin‐stimulated adenylate cyclase activities were greater in adult than young coronary sinus although the increment in isoproterenol‐stimulated adenylate cyclase activity in young tissue was greater when compared either with basal levels or expressed as a percentage of maximal catalytic activity. Both the traditional effector pathway of &bgr;‐adrenergic action, involving the stimulation of adenylate cyclase activity, and developmental changes in the action potential plateau may contribute to the developmental changes in delayed afterdepolarizations and triggered activity. (Circulation Research1989;65:325‐333)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;We studied relaxation during rapid rewarming of rabbit ventricular muscles that had been activated by rapid cooling. Rewarming from 1° to 30° C (in <0.5 second) activates mechanisms that contribute to the reduction of intracellular calcium concentration and thus relaxation (e.g., sarcoplasmic reticulum [SR] calcium pump and sarcolemmal Na‐Ca exchange and calcium pump). Rapid rewarming in normal Tyrode's solution induces relaxation with a half‐time (t1/2) of 217±14 msec (mean±SEM). During cold exposure, changing the superfusate to a sodiumfree, calcium‐free medium with 2 mM CoCl2(to eliminate Na‐Ca exchange) slightly slows relaxation upon rewarming in the same medium (t1/2=279±44 msec). Addition of 10 mM caffeine (which prevents SR calcium sequestration) to normal Tyrode's solution during cold superfusion slows relaxation somewhat more (t1/2=376±31 msec) than sodium‐free, calciumfree solution. However, if both interventions are combined (sodium‐free+caffeine) during the cold exposure and rewarming, the relaxation is greatly slowed (t1/2=2,580±810 msec). These results suggest that either the SR calcium pump or, to a lesser extent, sarcolemmal Na‐Ca exchange can produce rapid relaxation, but if both systems are blocked, relaxation is very slow. If muscles are equilibrated with 500 nM ryanodine before cooling, relaxation upon rewarming is not greatly slowed (t1/2=266±37 msec) even if sodium‐free, calcium‐free solution is applied during the cold and rewarming phases (t1/2=305±66 msec). This result suggests that ryanodine does not prevent the SR from accumulating calcium to induce relaxation. Relaxation in the presence of 10 mM caffeine appears to depend on a simple 3:1 Na‐Ca exchange since relaxation is slowed by extracellular sodium reduction but stays constant with simultaneous reduction of extracellular sodium concentration and extracellular calcium concentration (where [Na]3/[Ca] is held constant). Furthermore, relaxation in the presence of caffeine is slowed by membrane depolarization in a manner expected of a voltage‐sensitive Na‐Ca exchange. (Circulation Research1989;65:334‐342)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID