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Biomedical subjects

J T Shepherd

Publications and source records attributed to J T Shepherd.

At least 91 records · Page 5Linked to original sources
PubMed1981

Different behavior of the resistance vessels of the human calf and forearm during contralateral isometric exercise, mental stress, and abnormal respiratory movements.

Experiments were conducted in normal human volunteers to compare the response of the forearm and calf vessels to contralateral isometric exercise, mental stress, resisted breathing, coughing, and the Valsalva maneuver. Blood flows were measured by means of strain-gauge plethysmography, arterial blood pressure by auscultation, and heart rate by electrocardiography. Isometric exercise of one forearm (at one-third maximal voluntary contraction) for 90 seconds caused an increase in blood pressure and heart rate; the vascular resistance decreased in the resting forearm, and increased in the calf. The decrease in forearm resistance was greater with the subjects supine and attenuated with the subjects standing or reclining head-down. With arterial occlusion of the exercising forearm just prior to cessation of the handgrip, the blood pressure and the calf resistance remained elevated, while the heart rate returned to control. The forearm resistance increased during the occlusion period and remained elevated throughout it. Mental stress caused an increase in heart rate and blood pressure and a dilation of the forearm but not of the calf vessels; these changes were smaller in standing than in supine subjects. Resisted breathing and coughing caused an increase in heart rate and in forearm blood flow, but not in calf blood flow. The Valsalva maneuver was followed by decreases in blood flow to the upper and lower limbs. The different responses in forearm and calf vessels can be explained by a central component which triggers a vasodilator pathway (possibly cholinergic) which is distributed to forearm but not to calf vessels.

Adult↗
PubMed1980

The effects of acetylstrophanthidin and ouabain on the sympathetic adrenergic neuroeffector junction in canine vascular smooth muscle.

We performed experiments to determine the effects of acetylstrophanthidin (ACS) and ouabain on the adrenergic neuroeffector junction in dog saphenous veins. In quiescent strips incubated with 3H-norepinephrine (3H-NE), the drugs caused contraction and a progressive increase in overflow of 3H-NE and O-methylated metabolites; 3,4-dihydroxyphenylglycol (DOPEG) decreased. Tissue uptake of 3H-NE was partially inhibited. After surgical sympathectomy, both contraction and 3H-NE overflow were markedly attenuated. Following chemical sympathectomy with 6-hydroxydopamine, ouabain contractions were 11% of control, whereas the contractions due to exogenous norepinephrine were exaggerated. The initial overflow of 3H-NE was unaffected by tetrodotoxin, but the later and larger overflow with prolonged exposure was depressed. The former occurred in the absence of Ca2+, but the latter was Ca2+ dependent. Inhibition of the neuronal amine carrier by cocaine or desipramine and blockade of the neuronal alpha-adrenoceptors with phentolamine or phenoxybenzamine attenuated the release of 3H-NE evoked by ACS and ouabain. During electrical stimulation, ACS augmented the overflow of 3H-NE. This was attenuated by cocaine, desipramine, and the alpha-adrenolytic drugs. ACS, like pargyline, augmented the overflow of 3H-NE evoked by tyramine and depressed that of DOPEG. These experiments suggest that acetylstrophanthidin and ouabain (1) cause contraction of vascular smooth muscle by displacement of norepinephrine from neuronal stores, (2) reduce neuronal monoamine oxidase activity, (3) facilitate and may trigger Ca2+-dependent exocytotic release of norepinephrine, (4) partially inhibit the neuronal amine carrier mechanism but do not interfere with extraneuronal disposition of norepinephrine, and, finally (5) may have unexplained interactions with prejunctional alpha-adrenoceptors.

Animals↗
PubMed1980

Antidepressant drug action and presynaptic alpha-receptors.

Receptors have been demonstrated on the terminations of the sympathetic adrenergic nerves. One type, the so-called alpha 2-receptors, are activated by the norepinephrine that is released from the nerve terminals into the synaptic cleft; this activation causes a reduction in the output of the transmitter (negative feedback). Recent studies have demonstrated that certain antidepressant drugs can block these alpha 2-receptors and thus prevent their inhibitory action on the release of norepinephrine. If this occurs in the brain, the increases in norepinephrine levels could help explain the antidepressant action of these agents.

Animals↗
PubMed1980

Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein.

Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. We have investigated its effects on norepinephrine release from adrenergic nerves by using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]norepinephrine and mounted for superfusion, tension recording and the superfusate. Amitriptyline (10(-6); 5 x 10(-6) M) increased the overflow of [3H]norepinephrine but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decreased in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous norepinephrine, this indicates that the drug interacts with prejunctional alpha receptors. Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Thus, amitriptyline can increase the concentration of norepinephrine at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional alpha and muscarinic receptors. Since the cardiac adrenergic nerves also possess these receptors, the results could help to explain the cardiotoxic effects of the drug.

Amitriptyline↗
PubMed1979

Cardiac receptors: normal and disturbed function.

Widely distributed throughout the heart is a network of fibers connected to the medullary cardiovascular centers by nonmedullated vagal afferent fibers. When the traffic in these fibers is interrupted by vagal cooling, and the input from the arterial baroreceptors is prevented, the arterial blood pressure increases. Thus, these receptors act to inhibit tonically the vasomotor center. The receptors in the atria alter their rate of discharge with changes in atrial transmural pressure and contractility and are most active during end-inspiration and early expiration when the transmural pressure is maximal. The receptors in the ventricles respond to changes in ventricular end-diastolic pressure (preload), to the pressure generated during systole (afterload) and to changes in ventricular contractility. The cardiac mechanoreceptors have an equal or greater effect on the renal bed than the arterial mechanoreceptors and this effect is enhanced by hypercapnia. In animals, the cardiac mechanoreceptors have less control of the muscle vessels than the arterial mechanoreceptors, but the reverse is true in man. Both the cardiac and arterial mechanoreceptors can modulate the output of renin from the kidney, but the cardiac mechanoreceptors are more sensitive to small changes in blood volume. During coronary occlusion, in association with the bulging of the ischemic myocardium, the rate of discharge of these cardiac receptors is greatly increased.

Animals↗
PubMed1979

Interaction between neuronal amine uptake and prejunctional alpha-adrenergic receptor activation in smooth muscle from canine blood vessels and spleen.

Experiments were performed to determine the conditions in which norepinephrine release from adrenergic nerve terminals in smooth muscle from canine blood vessels and spleen might be inhibited by prejunctional alpha-adrenergic receptor activation. Strips of aorta, mesenteric and splenic arteries, splenic capsule and portal and saphenous veins were labeled with 7-3H-norepinephrine and mounted for superfusion. In the portal vein, an inhibitory effect of prejunctional receptor activation with exogenous norepinephrine (1.2 X 10(-6) M) on transmitter efflux could be demonstrated during electrical stimulation (9 V, 2 Hz) of the nerve terminals. By contrast, in the other tissues, inhibition of transmitter release during electrical stimulation or depolarization of the nerve terminals with K+ (40 mEq/l) could only be demonstrated aftet blockade of the neuronal uptake mechanism. That activation of prejunctional alpha-adrenergic receptors in blood vessels inhibits the exocytotic process is suggested by the failure of exogenous norepinephrine to affect either the basal efflux of 3-H-norepinephrine or the displacement of 3H-norepinephrine by tyramine.

Animals↗
PubMed1978

Increased reactivity of venous smooth muscle by small decreases in extracellular sodium.

In dog saphenous vein strips, decreases in extracellular sodium from 5% to 23% did not alter basal tension, but progressively increased tension developed during electrical stimulation (1.0 to 10 Hz). The augmentation did not occur with similar reductions in chloride ions. When osmolality was maintained with sucrose, the response to electrical stimulation also was enhanced with a 5% reduction in sodium ions, but did not increase further with larger sodium reductions. The enhancement was due to some effect on the smooth muscle cells, because the overflow of [7-3H]norepinephrine during electrical stimulation was unaffected by the sodium reduction, whereas contractions caused by norepinephrine and barium chloride were potentiated. The potentiation did not depend on increased influx of extracellular calcium, because contractions induced by acetylcholine were unaffected by sodium reduction; and after blocking calcium influx with verapamil, the norepinephrine contractions still were augmented. It was concluded that a decrease in extracellular sodium by 5% (from the normal value of 143.3--131.1 meq/1) can enhance the response of venous smooth muscle to adrenergic stimuli.

Acetylcholine↗
PubMed1978

Acetylcholine--inhibition of transmitter release from adrenergic nerve terminals mediated by muscarinic receptors.

The evidence is reviewed for the presence of muscarinic receptors on the sympathetic nerves to blood vessels. Activation of these receptors by acetylcholine in doses that are too small to affect the smooth muscle cells directly inhibits the release of norepinephrine evoked by electric impulses or potassium ions. This inhibitory action of acetylcholine is prevented by muscarinic blocking agents and is probably due to hyperpolarization of the adrenergic nerve terminals.

Acetylcholine↗
PubMed1978

Histamine and 5-hydroxytryptamine-inhibition of transmitter release mediated by H2- and 5-hydroxytryptamine receptors.

The vasodilatation caused by histamine and 5-hydroxytryptamine may be due, at least in part, to their inhibitory action on adrenergic neurotransmission. The evidence for this is as follows: 1) contractions of isolated canine vascular strips caused by sympathetic nerve stimulation are depressed by these substances whereas contractions caused by norepinephrine are either unchanged or augmented; 2) histamine and 5-hydroxytryptamine inhibit the release of norepinephrine evoked by sympathetic nerve stimulation of isolated vascular strips previously incubated with the labeled transmitter. This inhibitory effect can be demonstrated using concentrations of the substinces less than those required to affect the smooth muscle cells directly. By contrast, neither histamine nor 5-hydroxytryptamine inhibits the displacement of neuronal norepinephrine by tyramine, suggesting that these substances interfere with the exocytotic process. Additional studies have identified the histamine-H2 receptor as the probable mediator of this prejunctional action of histamine, whereas the nature of the receptor for 5-hydroxytryptamine remains to be clarified.

Animals↗
PubMed1978

Metabolic modulation of neurotransmitter release--adenosine, adenine nucleotides, potassium, hyperosmolarity, and hydrogen ion.

Evidence has accumulated that several factors, which have been proposed as mediators of exercise hyperemia, can modulate adrenergic neurotransmission in blood vessels. Adenosine and the adenine nucleotides depress the response of isolated blood vessels of the dog to nerve stimulation more than that to exogenous norepinephrine; this difference is explained by a decreased release of the neurotransmitter. Potassium, hyperosmolarity, and acidosis also depress adrenergic neurotransmission in isolated veins. These results are consistent with the hypothesis that metabolic changes in the vicinity of the adrenergic neuroeffector junction are capable of decreasing the output of neurotransmitter to the blood vessels in the exercising muscle.

Adenine Nucleotides↗