摘要:

The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously with aortic pressure and diameter. At constant suprathreshold pressure, NE had two dose-dependent effects. Inhibition was produced at low concentrations (10<SUP>-10</SUP>-10<SUP>-7</SUP>M), whereas excitation was produced at high concentrations (10<SUP>-6</SUP>-10<SUP>-5</SUP>M). Inhibition was attributed to BR unloading since the response was consistent with the fall in diameter, was mimicked by angiotensin II (10<SUP>-10</SUP>-10<SUP>-6</SUP>M), and was prevented by pretreatment with the smooth muscle relaxant sodium nitroprusside (10<SUP>-6</SUP>M) or the selective α<SUB>1</SUB>-adrenergic antagonist, prazosin (10<SUP>-6</SUP>M). Excitation was attributed to direct activation of the BR endings since this response was independent of changes in diameter, was not mimicked by angiotensin II, and was not prevented by sodium nitroprusside but was blocked by prazosin. These results indicate that NE has two modes of action, one mediated by contraction of local vascular smooth muscle and the other due to direct excitation of the nerve endings. It was also found that BR discharge at given diameters decreased more when pressure was lowered (smooth muscle passive) than when the aorta constricted (smooth muscle active). Furthermore, if diameter was held constant during smooth muscle contraction, discharge increased, as opposed to decreasing at constant pressure. These later results suggest that BR responses to vasoactive agents reflect not only changes in wall dimension but perhaps changes in wall tension and/or the coupling relation between BR and smooth muscle structures.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Prostaglandin E1(PGE1) inhibits a variety of functions of activated neutrophils including respiratory burst, release of leukotriene B4, and adherence to endothelial cells. To determine if PGE1alters the pathophysiology of complement-induced lung vascular injury, experiments were conducted in anesthetized sheep with lung lymph fistulas given a 1-hour infusion of zymosan-activated plasma. PGE, (30 ng/min/kg) or its saline vehicle was infused intravenously for 90 minutes beginning 30 minutes before the infusion of activated plasma. PGE, had no effect on leukocyte count, the initial hypoxemia and thromboxane A2release, or the development of acute pulmonary hypertension. However, PGE, prevented steady-state increases in lung lymph flow that in vehicle-treated sheep signaled an increase in lung microvascular permeability. Furthermore, extraction of PGE1by pulmonary endothelial cells was unaffected by the infusion of activated plasma. We propose that PGE1prevented the increase in lung vascular permeability by inhibiting adherence of activated neutrophils to endothelial cells.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The role of the autonomic nervous system in modulating reperfusion arrhythmias is still unclear. Experiments with sympathetic denervation or α- and β-adrenergic blocking agents have provided mixed results, while the effect of parasympathetic activation has not been investigated extensively. The effect of bilateral vagotomy and of vagal stimulation was studied, with and without attendant bradycardia, on the incidence of reperfusion arrhythmias in α-chloralose anesthetized cats. The left anterior descending coronary artery was occluded for 20 minutes, followed by reperfusion in 105 animals. The incidence and severity of reperfusion arrhythmias was compared in 1) neurally intact animals (heart rate 208 ± 24 beats/min), 2) animals with acute bilateral vagotomy (heart rate 233 ± 25 beats/min), 3) animals with vagal stimulation adjusted to maintain heart rate at 90-100 beats/min, and 4) animals with vagal stimulation + ventricular pacing to maintain heart rate at prestimulation values. All the neurally intact and vagotomized animals developed complex reperfusion arrhythmias, but these arrhythmias occurred in only 60 and 72%, respectively, of the animals with vagal stimulation and vagal stimulation + pacing (p < 0.005 vs. neurally intact and p < 0.02 vs. vagotomy). The incidence of ventricular fibrillation was similar in neurally intact (62%) and vagotomized (58%) animals; it was strikingly lower (7%, p <0.01) in animals with vagal stimulation when heart rate was allowed to decrease, and it was 48% when heart rate was kept constant during vagal stimulation. A selective protection from sustained (>30 seconds duration) ventricular tachycardia was observed in animals with vagal stimulation independent of heart rate changes. These data indicate that 1) suppression of tonic vagal activity, produced by bilateral vagotomy, does not modify the occurrence of complex reperfusion arrhythmias; 2) vagal stimulation initiated shortly before reperfusion significantly reduces the occurrence of complex reperfusion arrhythmias; 3) the protective effect against ventricular fibrillation is mediated primarily by the attendant decrease in heart rate; 4) sustained ventricular tachycardia is prevented by vagal stimulation independently of heart rate changes.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Muscarinic agonists can stimulate rather than inhibit cardiac muscle in some preparations. In left atria from hatched chicks, treatment with pertussis toxin reversed the membrane action of carbachol from hyperpolarization to depolarization and reversed the inotropic effect of carbachol from negative to positive. Acetylcholine also depolarized the membrane and increased the force of contraction in atria from pertussis-toxin-treated chicks although oxotremorine did not. These cholinergic responses were blocked by atropine but not by adrenoceptor antagonists, suggesting that they are mediated via muscarinic receptors and are not due to actions of endogenously released catecholamines. Muscarinic receptor stimulation leads to two distinct biochemical responses in chick atria: inhibition of adenylate cyclase and activation of phosphoinositide (PI) hydrolysis. The former is lost in atria from pertussis-toxin-treated chicks, whereas the PI response persists. The pharmacologic characteristics of the PI response resemble those of the depolarization and positive inotropic response. Both are insensitive to blockade by pertussis toxin, require high concentrations of carbachol, and are elicited by acetylcholine but not by oxotremorine. The present study suggests that muscarinic agonist-induced PI turnover may be responsible for the membrane depolarization and positive inotropic effects of carbachol and acetylcholine; that an increase in Na+conductance underlies these responses; and that it is stimulated either by an increase of intracellular calcium mobilized by inositol triphosphate and/or by activation by protein kinase C.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The vasodilating effects of flunarizine on smooth muscle strips of rabbit mesenteric artery have been investigated and compared with those of nifedipine. Flunarizine (30-300 nM) dose-dependently inhibited Ca2+-induced contractions in Ca2+-free solution containing 100 mM K+. Double reciprocal analysis showed that this inhibition was either competitive at low concentrations (30-100 nM; nifedipine-like) or noncompetitive at high concentrations (0.3-1 μM). The latter seemed to be partly related to an inhibition of contractile proteins as estimated from Ca2+-induced contractions in saponin-treated chemically skinned muscle strips. In contrast to the actions of nifedipine, flunarizine inhibited norepinephrine (NE)-induced contractions more than those induced by high K+, and at 0.3 μM, this agent totally blocked NE-induced contraction. Flunarizine also inhibited NE-induced contraction in Ca2+-free solution containing 2 mM EGTA. In Ca2+-free solution, NE rapidly hydrolyzed phosphatidylinositol 4,5-bisphosphate (PI-P2) and produced phosphatidic acid (PA). Flunarizine (30 and 300 nM), but not nifedipine (100 nM), inhibited NE-induced hydrolysis of PI-P2and production of PA. However, flunarizine (100 nM) did not modify the contraction induced by 10 μM inositol 1,4,5-trisphosphate in chemically skinned muscle strips. It is concluded that flunarizine inhibits both voltage-dependent (nifedipine-like) and receptor-operated Ca2+influx induced by NE and also inhibits NE-induced Ca2+release from intracellular stores due to inhibition of the hydrolysis of PI-P2.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The effects of atrial pacing on the left ventricular end-systolic pressure-volume relation, a relatively load-insensitive index of left ventricular performance, were studied in 8 chronically instrumented, conscious dogs. Six of the dogs were studied while autonomically intact, and 2 were studied after autonomic blockade with 2 mg/kg i.v. propranolol and 0.2 mg/kg i.v. atropine. Left ventricular pressure was measured with a micromanometer and left ventricular volume was determined from 3 ultrasonic orthogonal dimensions. Pressure was varied by caval occlusions at control heart rate and after atrial pacing at 100, 120, 140, 160, 180, and 200 bpm. The end-systolic pressure-volume relation was linear in every case (r=0.97 ± 0.03, SD). In the autonomically intact dogs, Emax, the slope of the end-systolic pressure-volume relation, was directly and monotonically related to heart rate in every dog, increasing to 238 ± 99% of control at peak pacing rate (p < 0.05). V0, the zero pressure intercept of the relation was also directly related to heart rate in every dog and increased 8.6 ± 5.5 ml from control to peak pacing rate (p < 0.05). Autonomic blockade did not attenuate these effects. This rightward shift of the end-systolic pressure-volume relation results in a reduced stroke volume from any end-diastolic volume, modulating the hemodynamic benefits of enhanced contractility. T, the time constant of isovolumic pressure fall during ventricular relaxation, was determined from beats with matched end-systolic pressures. T was related to heart rate, falling by 20 ± 10.3% over the range of rates studied in the autonomically intact dogs and by 23.1 ± 6.2% in the autonomically blocked dogs. Thus, the ventricle relaxes more rapidly at higher heart rates. We conclude that the frequency of contraction is concluded as an important determinant of overall pump function throughout the cardiac cycle in conscious dogs.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Sarcomere shortening and ultrastructure of intact isolated myocytes from ventricles of three-week-old and adult rabbits were examined. Cells were fixed and embedded, and after measuring their sarcomere shortening in response to electrical stimulation, they were examined in serial thin sections by electron microscopy. This structure-function analysis showed that adult cells were significantly larger, had longer rest sarcomere lengths, greater amount and velocity of sarcomere shortening, greater velocity of reextension, and shorter contraction duration than immature cells. In immature myocytes, a thin outer shell of myofibrils enveloped a central mass of mitochondria and nuclei, but in adult cells, the cytoskeleton divided the cell into compartments with the mitochondria arranged around and interspersed among the myofibrils. The different arrangement of the organdies and the cytoskeleton at the two ages may account for the shorter rest sarcomere length in the young myocytes and may confer differing internal loads that contribute to their smaller amount and velocity of sarcomere shortening. The corbular and longitudinal sarcoplasmic reticulum were less demarcated in immature than in adult cells. Myocytes from both ages showed postextrasystolic potentiation, suggesting that the sarcoplasmic reticulum modulates calcium at both ages. Restitution of contractility between contractions, obtained by measuring sarcomere shortening of interpolated extrasystoles, was faster in immature than in adult cells and may reflect the structural differences in the sarcoplasmic reticulum. The developmental differentiation in the sarcoplasmic reticulum suggests that changes in compartmentalization of calcium and in the distribution of putative calcium-release sites contribute to the increased contractility of adult myocytes.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID