Che Su

[3H]Adenosine Triphosphate: Release during Stimulation of Enteric Nerves

The isolated taenia coli of the guinea pig takes up tritiated adenosine, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate, in preference to tritiated inosine and adenine. After uptake, [3H]adenosine is converted and retained primarily as [3H]adenosine triphosphate. Tritium is released from taenia coli treated with [3H]adenosine upon activation of the nonadrenergic inhibitory nerves. These results are consistent with the previous evidence that adenosine triphosphate may be the transmitter from the nerves.

Electrical Quiescence of Pulmonary Artery Smooth Muscle During Sympathomimetic Stimulation

Simultaneous recordings of isometric tension and muscle membrane potential have been made in the sympathetic nerve-pulmonary artery preparation of the rabbit. The mean resting membrane potential recorded intracellularly was 51.5 mv. Sympathetic nerve stimulation and l-norepinephrine caused contraction without change in the membrane potential and in the absence of action potentials. Increase in extracellular potassium initiated both depolarization and contraction, although these two processes exhibited different latencies and time courses. The significance of these findings is discussed in relation to recent findings of dissociation in smooth muscle between contraction and membrane potential changes.

Comparison of Adrenergic Mechanisms in an Elastic and a Muscular Artery of the Rabbit

Elastic and muscular arteries are known to differ in function and in the magnitude of their response to vasoconstrictor influences. With the isolated thoracic aorta and ear artery of the rabbit as representative arteries, the morphological, physiological, and pharmacological correlates of these differences have been sought among their presynaptic adrenergic mechanisms. The adrenergic nerve plexus in the ear artery is wider and the nodes are denser than they are in the aorta. There is some evidence consistent with the hypothesis that the thicker the plexus, the greater the reuptake of released transmitter, the smaller the transmitter overflow, and the lower the efficiency of uptake of exogenous norepinephrine. Measurements of fractional release of tritiated norepinephrine suggest that qualitative differences in the adrenergic transmitter storage and release mechanisms may exist between the two vessels. Thus the considerable functional difference between the two vessels is in part, at any rate, a consequence of adrenergic mechanisms which differ both quantitatively and qualitatively from each other.

The bimodal basis of the contractile response of the rabbit ear artery to norepinephrine and other agonists

Abstract Strips of rabbit ear artery exhibit biphasic contractile responses to l-norepinephrine (1-NE), histamine, and serotonin. Evidence is presented on the basis of an analysis of the response to 1-NE that the two phases of contraction are associated with different modes of excitation and can be influenced independently. The initial part of the response is phasic. The response after 4 sec agonist exposure is the same as that after 32 sec. It is probably associated with local radial propagation of excitation in that the initial excitatory period is short, the contraction is preceded by electrical change and is abolished upon tissue exposure to a solution in which all NaCl and KCl is replaced by potassium methylsulfate. In contrast the second contractile phase is related to the time of tissue exposure to the drug, is an equilibrium-like response and is not dependent upon cell membrane polarization. Since this phase is more affected by calcium depletion than the first, the sources of activator calcium for the two phases may be different: that for the first phase many originate predominantly from intracellular and that for the second from extracellular sources. These findings support the hypothesis that the biphasic contractile response of the vessel reflects two different modes of excitation of the muscle wall by the agonists: the first, a triggered, propagated event; the second, a slow, equilibrium-type, non-propagated response.

Analysis of changes in reactivity of rabbit arteries and veins two weeks after induction of hypertension by coarctation of the abdominal aorta.

Vessel dimensions and characteristic responses to norepinephrine were measured in various arteries and veins of the rabbit made hypertensive by partial constriction of the upper abdominal aorta. The ear, radial, and basilar arteries taken from the circulation proximal to the ligature (the hypertensive arteries) were thickened in proportion to the rise in arterial blood pressure. The water, sodium, and potassium contents of these and all other vessels were not significantly changed in the hypertensive rabbits. The maximum response to norepinephrine in the ear artery, a representative vessel from the hypertensive part of the rabbit, was increased, whereas the sensitivity of this vessel to norepinephrine expressed as the ED50 did not alter with changes in the arterial blood pressure. In contrast, the thickness and the maximum response to norepinephrine of the saphenous artery, representative of vessels distal to the ligature (normotensive vessels) and of the saphenous and cephalic veins were unaltered. The sensitivity as indicated by the norepinephrine ED50 of the veins, but not of the saphenous artery, increased with a rise in carotid artery blood pressure. These results suggest that the increased responsiveness to norepinephrine of arteries proximal to the ligature is due to changes in muscle mass and that the increased responsiveness of the veins is due to increased sensitivity to norepinephrine.

Evidence for an increase in adrenergic nerve function in blood vessels from experimental hypertensive rabbits.

The possibility of changes in the adreaergic innervation of blood vessels in experimental hypertension was investigated by measuring arterial norepinephrine content, neuronal uptake of norepinephrine, and the neurogenic contractile response in rabbits made hypertensive by partial constriction of the abdominal aorta proximal to the kidneys. Two to 3 weeks after surgery, norepinephrine content was increased in the arteries above the ligature, where arterial blood pressure was increased, but not in the arteries below the ligature, where arterial blood pressure was normal, in the heart, or in the veins. Neuronal norepinephrine uptake per unit length of vessel and the neurogenic contractile response increased with the rise in arterial blood pressure. The neurogenic contractile response can be taken as an indication of an increase in transmitter release. These results taken together suggest an increase in the function and possibly the amount of the adrenergic neuronal terminal in hypertension. Since the distributions of the changes in the adrenergic innervation and the increases in smooth muscle cell proliferation in hypertension are similar, these two processes may be interrelated.

Innervation Pattern and Neurogenic Response of Rabbit Veins

The adrenergic neuroeffector mechanism has been assessed in 14 different veins of the rabbit chosen to represent vessels of different, function and regional location. The pattern, distribution and den

Development of neuroeffector mechanisms in the carotid artery of the fetal lamb.

A survey has been made of mechanisms associated with vascular adrenergic neuroeffector transmission in the lamb fetuses between 53 days and term gestation. The common carotid artery was isolated for studies of enzymic activities, uptake of norepinephrine (NE) and reactivity to vasoactive agents. The extra-neuronal NE uptake, monoamine oxidase and catechol-O-methyltransferase activities were present in the carotid artery of the youngest fetuses. The contractile responses to NE and serotonin and neuronal NE uptake preceded the response to adrenergic nerve stimulation during fetal growth. These results suggest that the mechanisms for adrenergic transmitter inactivation, transmitter action on vascular smooth muscle cells, and neuronal transmitter delivery develop in that sequence.

Functional studies of the small pulmonary arteries

Abstract Based upon catecholamine histofluorescence and capacity for neuronal uptake of norepinephrine, extra- and intrapulmonary arteries are well supplied by adrenergic nerves. In isolated segments of arteries larger than 0.6 mm in diameter, these nerves release sufficient transmitter to cause vasoconstriction. However, in arteries smaller than 0.6 mm in diameter, both nerve stimulation and NE application elicited either very small responses or none at all. The vascular smooth muscle was responsive under the experimental conditions, since all arterial segments constricted in response to 5HT, histamine, and KCl, and the maximal effects of the three agents were equal. It is not yet known whether the poor reactivity of small arteries to NE and adrenergic nerve stimulation is peculiar to the rabbit pulmonary vascular bed, and whether segments of the pulmonary vascular tree farther downstream than those studied are more reactive to sympathetic stimulation. Possibly the sympathetic control of vascular tone is restricted to the relatively large arteries. Reduction in the magnitude of the contractile response, rather than sensitivity to NE, appears to account for the diminution of vessel response as the vessel becomes smaller. It is speculated that, in the pulmonary vasculature through which the output of the right heart passes to the left, an extensive arterial constriction accompanying sympathetic discharge resulting in major changes in blood flow is undesirable.

Distribution Theory of Resistance of Neurogenic Vasoconstriction to Alpha-Receptor Blockade in the Rabbit

The effects of α-receptor-blocking agents on the contractile responses of isolated rabbit arteries to sympathetic nerve stimulation and exogenous l-norepinephrine (l-NE) were compared. In the pulmonary artery and aorta, yohimbine, phentolamine, and phenoxybenzamine blocked the response to nerve stimulation less than that to an equipotent dose of l-NE. This resistance of neurogenic response was independent of the frequency and number of stimuli and persisted after inhibition of the nerve l-NE uptake by cocaine. The neurogenically released transmitter l-NE probably forms a high concentration near the adventitia-media junction, whereas the exogenous NE is distributed evenly throughout the thickness of media. Thus higher concentrations of α-receptor-blocking agents would be needed to block the effect of neurogenic l-NE than to block that of exogenous l-NE. This explanation of the resistance was thought to be more appropriate to the large vessels tested than that based on neuroeffector proximity.