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Biomedical subjects

J T Shepherd

Publications and source records attributed to J T Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1989

Ammonium ions cause relaxation of isolated canine arteries.

Experiments were designed to determine the mechanism of action underlying relaxation of vascular smooth muscle induced by ammonium ions. In particular, the possibility that these ions might be an endothelium-derived relaxing factor was examined. Rings of large canine femoral, mesenteric and coronary arteries and of small arteries from the gracilis muscle were suspended in organ chambers for the recording of isometric force. Membrane potential was recorded with intracellular microelectrodes in smooth muscle cells from the mesenteric artery. Ammonium ions induced relaxation which were independent of the presence of the endothelium. The relaxations were not prevented by adrenergic, serotonergic, muscarinic and histaminic blockers, by scavengers of oxygen-derived radicals or by inhibitors of soluble guanylate cyclase. The relaxations were prevented by a decrease in extracellular calcium concentration and by inhibition of the Na+/K+ pump. The results are compatible with the hypothesis that the relaxation induced by ammonium ions is related to changes in intracellular pH and, at high concentration of these ions, possibly to activation of the Na+/K+ pump. Ammonium ions are neither the endothelium-derived relaxing factor which activates guanylate cyclase nor the factor that induces endothelium-derived hyperpolarization. Inasmuch as relatively low concentrations of the ion induce relaxation of small arteries of skeletal muscle, they could contribute to exercise hyperemia.

Animals↗
PubMed1988

Vasoconstriction induced by ouabain in the canine coronary artery: contribution of adrenergic and nonadrenergic responses.

Ouabain, when applied to rings of the left circumflex coronary artery of the dog (which contains both alpha 1-adrenoceptors leading to contraction and beta 1-adrenoceptors leading to relaxation) caused an initial contraction which peaked within 15 minutes and a later secondary increase in tension which peaked within 60 minutes. These contractions were prevented by Ca2+ removal or by verapamil. Adrenergic denervation with 6-hydroxydopamine did not affect the initial contraction. Thus it is due to a nonadrenergic effect of the glycoside. Since the secondary increase in tension was prevented by adrenergic denervation and prazosin, it is likely to be due to norepinephrine released from adrenergic nerves acting on alpha-adrenoceptors. This interpretation was confirmed by the finding that ouabain, after a latent period of about 35 minutes, augmented the output of 3H-norepinephrine from helical strips of the artery previously incubated with tritiated transmitter. In rings contracted with prostaglandin F2 alpha, ouabain reduced beta-adrenergic relaxations caused by isoproterenol or exogenous norepinephrine, but not those caused by sodium nitroprusside. Thus, in this artery, ouabain depresses the responses of the beta-adrenoceptors to the norepinephrine which it releases, thereby permitting the neurotransmitter to cause contraction by activating postjunctional alpha 1-adrenoceptors.

Animals↗
PubMed1988

Potassium-induced endothelium-dependent rhythmic activity in the canine basilar artery.

Rings of canine basilar arteries with and without endothelium were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution. Increased extracellular concentrations of potassium (3-20 mM) caused rhythmic activity in rings with endothelium. This activity was reduced by the removal of the endothelium and by exposure to indomethacin, meclofenamate, diltiazem, or ouabain; it was not affected by tetrodotoxin, bretylium tosylate, phentolamine, propranolol, atropine, methiothepin, and cimetidine. Prostaglandin F2 alpha and E2 caused concentration-dependent increases in the frequency and the amplitude of this rhythmic activity and reversed the inhibitory effect of indomethacin and meclofenamate. Prostacyclin abolished the activity. These results suggest that increasing the concentration of extracellular potassium causes rhythmic activity in canine basilar arteries because of the production and/or release by the endothelium of products of cyclooxygenase such as prostaglandin F2 alpha and E2. These may initiate the contraction while prostacyclin triggers the relaxation phase of the rhythmic activity, possibly by activating Na+, K+-ATPase of the vascular smooth muscle.

Animals↗
PubMed1988

Reflex constriction of human limb resistance vessels to head-down neck flexion.

The effect of head-down neck flexion on forearm and calf blood flow was determined in 10 healthy male subjects. The subject lay prone, with the neck slightly extended and the chin resting on a soft-padded support at the edge of the table. The chin support was then removed, and the subject maximally flexed and lowered the neck. This was followed by return to the initial position. Neck flexion caused a rapid decrease in blood flow in both forearm and calf; at 30 s this averaged 39 and 35%, respectively. The flow in both forearm and calf gradually recovered as the neck flexion was sustained and approached the control values at the end of 10 min. The blood flow at the ankle was unchanged, indicating that the decrease occurred in the skeletal muscles. The arterial blood pressure and heart rate were unchanged; thus the decrease in flow was due to vasoconstriction. The fact that the decrease was evident as soon as the head was lowered indicated that it was nervously mediated. Neither contraction of the flexor muscles of the neck nor venous congestion of the head, in the absence of the head-down position, altered the blood flow. Although the mechanism of the decrease in flow has not been determined, the studies demonstrate that in response to certain stimuli, the resistance vessels in the skeletal muscles of the forearm and calf undergo a similar nervously mediated vasoconstriction.

Forearm↗
PubMed1988

Endothelium-dependent contractions to calcium ionophore A23187, arachidonic acid, and acetylcholine in canine basilar arteries.

The effects of the calcium ionophore A23187, arachidonic acid, and acetylcholine were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in physiological saline. In unstimulated rings, A23187, arachidonic acid, and acetylcholine caused endothelium-dependent contractions. The contractions of rings caused by uridine 5'-triphosphate were not affected by removal of the endothelium. An inhibitor of cyclooxygenase, indomethacin (10(-5) M), prevented excitatory responses to A23187, arachidonic acid, and acetylcholine but did not alter contractions caused by KCl. An inhibitor of thromboxane synthetase, dazoxiben (10(-4) M), significantly reduced endothelium-dependent contractions to A23187 and arachidonic acid but did not significantly affect contractions caused by acetylcholine. These results demonstrate that A23187, arachidonic acid, and acetylcholine cause excitatory endothelium-dependent responses in canine cerebral blood vessels by increasing the release of product(s) of cyclooxygenase from endothelial cells; in the case of A23187 and arachidonic acid, thromboxane A2 contributes to the endothelium-dependent contractions.

Acetylcholine↗
PubMed1988

The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins.

The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.

Animals↗
PubMed1987

Inorganic phosphate inhibits sympathetic neurotransmission in canine saphenous veins.

Inorganic phosphate has been proposed as the initiator of metabolic vasodilatation in active skeletal muscle. The present study was primarily designed to determine if this substance has an inhibitory effect on adrenergic neurotransmission. Rings of canine saphenous veins were suspended for isometric tension recording in organ chambers. A comparison was made of the ability of inorganic phosphate (3 to 14 mM) to relax rings contracted to the same degree by electrical stimulation, exogenous norepinephrine, and prostaglandin F2 alpha. The relaxation during electrical stimulation was significantly greater at all concentrations of phosphate. In strips of saphenous veins previously incubated with [3H]norepinephrine, the depression of the contractile response caused by phosphate during electrical stimulation was accompanied by a significant reduction in the overflow of labeled neurotransmitter. Thus inorganic phosphate inhibits sympathetic neurotransmission and hence may have a key role in the sympatholysis in the active skeletal muscles during exercise. By contrast, in this preparation, it has a modest direct relaxing action on the vascular smooth muscle.

Animals↗
PubMed1987

Endothelium-dependent contraction to stretch in canine basilar arteries.

Stretch applied to isolated canine basilar arteries caused the development of active tension in rings with endothelium but not in those in which the endothelium had been removed. Blockade of calcium entry with diltiazem or inhibition of cyclooxygenase with indomethacin abolished the endothelium-dependent response to stretch. These observations suggest that the endothelium may contribute to the autoregulation of cerebral blood flow during increases in transmural pressure by the increased production and/or release of prostaglandins, which causes activation of the underlying vascular smooth muscle.

Animals↗
PubMed1987

Postural cardiovascular reflexes: comparison of responses of forearm and calf resistance vessels.

Simultaneous measurements were made of changes in vascular resistance in the forearm and calf in response to moving from supine to sitting or to head-down tilt. The subjects were healthy male volunteers, 21-63 yr. Blood flows were measured by venous occlusion plethysmography using mercury-in-Silastic strain-gauges. The gauges were maintained at the same level relative to the heart during the postural changes. Arterial blood pressure was measured by auscultation; heart rate was counted from the plethysmograms. Changing from supine to sitting caused a decrease in forearm blood flow from 4.13 +/- 0.14 to 2.16 +/- 0.19 ml.100 ml-1.min-1. Corresponding calf flows were 4.21 +/- 0.32 and 4.40 +/- 0.59 ml.100 ml-1.min-1. There was no change in mean arterial blood pressure, and heart rate increased by 8.0 +/- 1.5 beats/min. Arrest of the circulation of both legs with occlusion cuffs on the thighs before sitting, to prevent pooling of blood in them, reduced the degree of forearm vasoconstriction. Neck suction (40 Torr) during sitting, to oppose the decrease in transmural pressure at the carotid sinuses, inhibited the vasoconstriction. During a 30 degrees head-down tilt, there was a dilatation of forearm but not of calf resistance vessels. A Valsalva maneuver caused a similar constriction of both vascular beds. Thus, when changes in vascular resistance in forearm and calf are compared, the major reflex adjustments to changes in posture take place in the forearm.

Adult↗
PubMed1987

Human postjunctional alpha-1 and alpha-2 adrenoceptors: differential distribution in arteries of the limbs.

Experiments were performed in order to characterize the post-junctional alpha adrenoceptors that mediate contraction in arteries of human limbs. Blood vessels were obtained from patients undergoing amputation of an extremity for reasons other than vascular disease. Proximal (dorsalis pedis and arcuate arteries of the foot, superficial palmer arch of the hand) and distal (digital arteries of the foot and hand) blood vessels were studied from each limb. The blood vessels were removed within 60 min of amputation and were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution. In proximal and distal arteries, alpha-1 adrenergic blockade with prazosin produced a nonparallel shift in the concentration-effect curve to high compared to low concentrations of the agonist. In contrast, alpha-2 adrenergic blockade with rauwolscine was more effective against responses evoked by low concentrations of norepinephrine. This suggests that the alpha-2 adrenergic component of the response to norepinephrine is a low-maximum effect compared to the alpha-1 adrenergic component. Prazosin was less potent and rauwolscine more potent in distal arteries, compared to proximal arteries which might indicate an increased alpha-2 adrenergic response in distal arteries. The selective alpha-1 adrenergic agonist, phenylephrine, produced similar responses in proximal and distal arteries. However, the selective alpha-2 adrenergic agonist, B-HT 920, caused greater contractile responses in distal arteries compared to proximal arteries. The results suggest that alpha-1 and alpha-2 adrenoceptors are present on the vascular smooth muscle of arteries of human limbs, and that alpha-2 adrenoceptors are more prominent on distal arteries. This may be related to an increased contribution of the distal arteries to thermoregulation.

Arm↗
PubMed1987

Circulatory response to exercise in health.

Engagement in muscular exercise involves complex local and nervous adjustments of the circulation. In the active muscles, including cardiac muscle, the resistance vessels relax in response to local chemical changes to provide an increase in blood flow adequate for their metabolic requirements. There is increased release of norepinephrine from the sympathetic nerve endings as a result of increased sympathetic outflow; the resultant alpha-receptor activation leads to constriction of both systemic resistance and capacitance vessels outside the active muscles, and the beta-receptor activation leads to an increase in heart rate, shortening of the refractory period, and enhancement of myocardial contractility. As a consequence, the filling pressure of the heart and arterial blood pressure are maintained, and the increase in left ventricular output is directed primarily to the active muscles. During upright exercise, the action of the leg muscle pump contributes to the maintenance of the cardiac filling pressure. As exercise continues and body temperature rises, the skin flow increases to dissipate heat from the body. Static exercise causes a greater increase in arterial blood pressure than dynamic exercise. This is due to the combination of an increase in cardiac output and in total systemic vascular resistance as a consequence of increase sympathetic outflow and mechanical compression of the vessels in the active muscles. The hemodynamic changes result from activation of ergoreceptors in the contracted muscles and from central command. The increase in pressure helps to oppose the mechanical compression. The arterial baroreceptors are reset so that they operate normally around the higher blood pressure.

Adult↗
PubMed1986

Mechanisms responsible for coronary vasospasm.

Studies have been conducted on isolated segments of the left circumflex coronary artery of the dog to gain information on the mechanism or mechanisms of vasospasm. Coronary arteries contain both postjunctional alpha 1- and beta 1-adrenoceptors, and both are accessible to norepinephrine released from the sympathetic nerves. However, owing to the dominance of the beta 1-adrenoceptors, sympathetic stimulation causes relaxation of the vascular smooth muscle. In the primary branches of the circumflex artery, only beta 1-adrenoceptors are present. In patients with spasm of the coronary arteries, blockade of the beta 1-adrenoceptors may aggravate the spasm by permitting the unopposed constrictor action of the sympathetic nerves on the alpha 1-adrenoceptors on these vessels. The blood platelets contain substances, including 5-hydroxytryptamine (serotonin) and thromboxane A2, which can cause constriction of vascular smooth muscle. These substances are released whenever platelets aggregate. The normal endothelium, by forming and releasing prostacyclin, inhibits platelet aggregation. In addition, in response to platelet products, the normal endothelium forms one or more inhibitory substances that cause relaxation of the underlying smooth muscle. Also, if any thrombin is formed, this also causes an endothelium-mediated relaxation of the artery. Patients with coronary artery spasm usually have morphologic changes in the artery at the site of the spasm. Thus, platelets can aggregate at the site and the resultant release of serotonin and thromboxane A2, acting directly on the smooth muscle, causes constriction of the artery. Hypoxia of the myocardium follows and this augments the constriction.

Adenosine Diphosphate↗
PubMed1986

Effect of vibration on a canine cutaneous artery.

Vibration of rings of isolated canine saphenous arteries depressed contractions induced by potassium chloride, prostaglandin F2 alpha, and activation of the adrenergic nerve endings by electrical stimulation. Peak contractions to exogenous norepinephrine were not significantly affected by vibration, being augmented, unchanged, or depressed, whereas contractions during the stable plateau phase were depressed. The calcium entry blocker diltiazem reduced the peak response but not the stable plateau phase of the contraction to norepinephrine; in the presence of diltiazem, vibration still depressed the latter. When vibration was applied during the steady state of contractions evoked by electrical stimulation, the depression was immediate, and its extent increased with both the amplitude (0.025-0.10 mm) and the frequency (30-150 Hz) of vibration. In arteries labeled with [3H]norepinephrine, vibration (120 Hz, 0.1 mm amplitude) during electrical stimulation induced a slight but significant increase in the release of labeled transmitter. It is suggested that the depression of contractions to potassium ions, prostaglandin F2 alpha, sympathetic nerve stimulation, and the plateau phase of the response to exogenous norepinephrine are caused by vibration depressing the force-generating process in vascular smooth muscle. Failure of vibration to significantly depress the peak contraction to norepinephrine may be explained by the facilitation by vibration of the influx of extracellular calcium ions.

Animals↗
PubMed1986

Differential effects of lower body negative pressure on forearm and calf blood flow.

Modest degrees of lower body negative pressure (less than 20 mmHg) cause a reflex constriction of forearm resistance vessels attributable to a decrease in activity of cardiopulmonary mechanoreceptors. In the present study, we sought to determine whether the calf vessels respond similarly. Left forearm and right calf blood flows were measured simultaneously by strain-gauge plethysmography in 10 healthy volunteers. Forearm flows decreased significantly from control during negative pressures of 10, 15, or 20 mmHg, whereas calf flows did not decrease significantly until 20 mmHg; at 10, 15, and 20 mmHg, decreases in forearm flow were significantly greater than those of the calf. Similar results were obtained in a second series of experiments in which venous pooling in the right leg during lower body negative pressure was prevented by enclosing it in a boot. At 40 mmHg, or after a Valsalva maneuver, both forearm and calf vessels constricted markedly and to the same degree. It appears that the reflex reduction in blood flow to the skeletal muscles of the limbs resulting from deactivation of the low-pressure intrathoracic mechanoreceptors is directed primarily to the arm.

Adult↗