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Biomedical subjects

J T Shepherd

Publications and source records attributed to J T Shepherd.

At least 109 records · Page 6Linked to original sources
PubMed1978

Role of the venous system in circulatory control.

The systemic venous system is a dynamic component of the cardiovascular system, and it has a key role in the maintenance of the appropriate filling of the chambers of the heart and hence of the stroke volume. Studies in man and animals have characterized the different mechanisms that control the three major components--the splanchnic, muscle, and cutaneous vascular beds--and have provided information on the changes caused by disease and by chemical agents. Concerning man, much of the information has of necessity been derived from the behavior of the limb veins, the control of which is different from that of the splanchnic capacitance vessels. Studies of the behavior of the splanchnic capacitance vessels are needed before the action of drugs that affect the cardiovascular system of man is fully understood.

Adrenal Gland Neoplasms↗
PubMed1977

Anodal block of medullated cardiopulmonary vagal afferents in cats.

In anesthetized cats examination was made of the conditions under which the application of DC current to a mixed nerve permits determination of whether a reflex response is mediated by medullated or nonmedullated afferents. The following precautions should be observed. The nerve must be stripped of its sheath and bleeding avoided. The anode should be 6 mm distant from the cathode. The temperature of the mineral oil surrounding the nerve should be 30-32 degrees C to avoid activation of nonmedullated fibers during the block. The major limitation is a time- and frequency-dependent block of nonmedullated fibers which makes the technique suitable only for differentiating between medullated fibers and nonmedullated fibers with low frequency traffic. Observing these criteria, anodal block of the cervical vagus in sino-aortic denervated cats resulted in a mean rise in aortic pressure of 8 Torr; subsequent cold block caused a further mean rise of 30 Torr. Thus 80% of the total increase in aortic pressure could be ascribed to interruption of vagal C-fiber activity.

Afferent Pathways↗
PubMed1977

Inhibition of sympathetic neurotransmission in canine blood vessels by adenosine and adenine nucleotides.

Adenosine and the adenine nucleotides caused a greater relaxation of strips of canine saphenous vein and tibial artery when they had been contracted by nerve stimulation than by exogenous norepinephrine. An infusion of adenosine into the dogs' lateral saphenous vein, perfused at constant flow, caused a greater relaxation of this vein when constricted by electrical stimulation of the lumbar sympathetic chain than by exogenous norepinephrine. That this difference was due to inhibition by these compounds of the output of neurotransmitter from the sympathetic nerve endings was demonstrated by column chromatographic analysis of the radioactivity in the superfusion fluid of vein strips, previously incubated with tritiated norepinephrine. Both adenosine and adenosine triphosphate (10(-5) M) reduced the efflux of 3H-norepinephrine during nerve stimulation with electrical impulses. Adenosine also reduced the efflux caused by potassium (30 mM), but not that caused by tyramine (6 X 10(-6) M). Theophylline antagonized the inhibitory effect of adenosine on the sympathetic neurotransmission. We found that at 4 X 10(-4) M adenosine triphosphate still caused a decreased efflux of neurotransmitter during electrical stimulation, but with adenosine the 3H-norepinephrine efflux no longer decreased and the overflow of deaminated compounds increased. Furthermore, the same concentration of adenosine increased the efflux of 3H-norepinephrine and deaminated compounds in unstimulated strips, and the increase of 3H-norepinephrine was enhanced after monoamine oxidase inhibition. Thus, we conclude that at higher concentrations adenosine increases the intraneuronal leakage of norepinephrine out of the storage vesicles.

Adenine Nucleotides↗
PubMed1977

Behavior of cardiac receptors with nonmyelinated vagal afferents during spontaneous respiration in cats.

Activity from left atrial and left ventricular receptors with nonmyelinated vagal afferents (mean conduction velocity, 1.2 m/sec) was recorded in 13 closed-chest spontaneously breathing cats anesthetized with alpha-chloralose. The anatomic position of each receptor was determined by probing the opened heart at the conclusion of the experiment. Three of eight left atrial receptors and four of five left ventricular receptors were silent under resting conditions. The mean discharge frequency under resting conditons for the six receptors displaying spontaneous activity was 1.0 +/- 0.15 impulse/sec. Thus cardiac receptors with vagal nonmyelinated afferent have a low resting discharge in spontaneously breathing cats. The frequency and pattern of discharge of atrial but not of ventricular receptors was altered during spontaneous respiration. The atrial receptors discharged with cardiac rhythmicity during end inspiration and early expiration when transmural pressure was greatest and were silent for the remainder of the respiratory cycle. Whe respiration was augmented by CO2 breathing or blood volume was increased, the rate of discharge was a linear function of atrial transmural pressure. Eleven ventricular receptors with nonmyelinated afferents (mean conduction velocity, 1.0 m/sec) were exposed to graded volume expansion and phenylephrine infusion in eight open-chest and three spontaneously breathing cats. Raising left ventricular end-diastolic pressure alone increased the frequency of discharge, and a concomitant increase in systolic pressure caused a further increase in firing.

Animals↗
PubMed1976

Interplay among carotid sinus, cardiopulmonary, and carotid body reflexes in dogs.

Interactions among vascular reflexes evoked from carotid sinuses, carotid bodies, and cardiopulmonary region were examined in anesthetized, atropinized, and respired dogs with aortic nerves cut. The carotid sinuses were perfused at 220, 150, and 40-50 mmHg; the chemoreceptors were stimulated by perfusion with hypoxic hypercapnic blood. Cardiopulmonary vasomotor inhibition was interrupted by vagal cold block. Measurements were made of arterial blood pressure and of kidney and hindlimb vascular resistance. At sinus pressures less than 170-160 mmHg, cardiopulmonary vasomotor inhibition increased with increase in blood volume. At high sinus pressure, interruption of this augmented cardiopulmonary inhibition was as ineffective in changing vascular resistance as interruption of the lesser inhibition present during normovolemia. Chemoreceptor stimulation increased the response to vagal block at intermediate but not at high or low sinus pressure. The studies demonstrate the dominant role of the carotid sinus reflex when the three systems interact and the ineffectiveness of chemoreceptor stimulation when carotid or cardiopulmonary inhibition is maximal.

Animals↗
PubMed1976

Hyperosmolarity: effects on nerves and smooth muscle of cutaneous veins.

Helical strips from dogs' saphenous veins were mounted in an organ bath (Krebs-Ringer solution, 37 degrees C) for isometric tension recording. Additional strips were incubated with [7-3H]norepinephrine and mounted for superfusion and isometric tension recording. The perfusate was collected every 2 min for estimation of total radioactivity and for column chromatographic separation of [3H]norepinephrine and its metabolites. Increasing osmolarity by sucrose caused a slow contraction that was maximal at 500-550 mosM and was accompanied by a reduction in total 3H efflux. The contraction was unaffected by a Ca2+-free medium, alpha-adrenegic blockade, and beta-adrenergic stimulaton. It was depressed by cooling (29 degrees C) and by anoxia combined with a glucose-free medium. Contractions elicited by K+ and Ba2+ were augmented by hyperosmolarity, but those caused by sympathetic nerve stimulation, tyramine, and norepinephrine were depressed. The output of [3H]norepinephrine during nerve stimulation was reduced. Thus, the hyperosmolarity causes 1) contraction of vascular smooth muscle, 2) augmentation of the contractile response to K+ and Ba2+, 3) depression of the excitation caused by norepinephrine, and 4) inhibition of the neuronal release of norepinephrine.

Animals↗
PubMed1976

Role of heart and lung receptors with nonmedullated vagal afferents in circulatory control.

Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed that receptors in the lungs, the atria, and the ventricles each are responsible for the vasomotor inhibition. That this inhibition is due to nonmedullated vagal afferents (C fibers) was demonstrated by selective cooling of the vagi, anodal block of medullated afferents, and selective electrical stimulation of medullated and nonmedullated fibers. In the open-chest cat the discharge frequency of individual C fibers is sparse and irregular (mean, 1.4 impulses/sec) but increases to 10 or more impulses/sec with moderate increases in cardiac filling pressure and exhibits cardiac rhythmicity or is continuous throughout the cardiac cycle. The inhibition of sympathetic vasomotor outflow effected through the cardiopulmonary receptors is inversely related to that exerted by the arterial baroreceptors. The former receptors have less influence on the muscle circulation than the latter, but have an equal or greater effect on the renal circulation. In summary, receptors in the heart and lungs with nonmedullated vagal afferents are an important component of the integrated neural control of the circulation.

Action Potentials↗
PubMed1976

Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.

Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.

Animals↗
PubMed1976

Effect of nitroprusside on smooth muscle and adrenergic nerve terminals in isolated blood vessels.

Experiments were designed to assess the mode of action of nitroprusside on isolated blood vessels and its relative potency on venous and arterial smooth muscle. Strips from dog blood vessels were mounted in an organ bath for isometric tension recording. Sodium nitroprusside (10(-5) M) depressed the contraction of saphenous vein strips caused by electric stimulation, tyramine, K+, Ba++, norepinephrine and acetylcholine. The depression of the norepinephrine-induced contractions also occurred in a Ca++- free medium and when Ca++ influx was inhibited by verapamil. Nitroprusside reduced the frequency of the spontaneous contractions of strips of portal-mesenteric veins. It depressed the contraction caused by norepinephrine in tibial artery strips more than in saphenous vein strips. Saphenous vein strips were incubated with (3H)norepinephrine and mounted for superfusion and isometric tension recording. Sodium nitroprusside (10(-5) M) had no effect on the basal efflux of 3H compounds. During electric stimulation, it did not change the output of (3H)norepinephrine but increased the outflow of deaminated and O-methylated metabolites. Thus sodium nitroprusside 1) has a direct effect on the smooth muscle cells which is independent of Ca++ influx, 2) depresses contractions of different types of vascular smooth muscle and 3) does not inhibit the release of norepinephrine from the nerve endings.

Animals↗
PubMed1975

Control of high and low blood pressure in the dog by aortic and sinus nerves.

1. Changes in afferent activity in the aortic and sinus nerves with alterations of blood pressure were studied in anesthetized dogs. Mean aortic blood pressure was changed from 220 to 50 mmHg by using a pressurized reservoir connected to the abdominal aorta. 2. The stimulus--response curve (defined by measuring the mean impulse frequency at various pressures) from both nerves was S-shaped; the curve for the aortic nerve was shifted to the right of the sinus nerve curve. 3. In the dog, the aortic arch baroreceptors act predominantly as an anti-hypertensive mechanism; at lower pressures, the major control occurs through the sinus baroreflex.

Afferent Pathways↗
PubMed1975

Relative influence of carotid baroreceptors and muscle receptors in the control of renal and hindlimb circulations.

In vagotomized dogs, a comparison was made of the relative ability of the carotid baroreceptors and of the receptors in skeletal muscles to cause constriction of the renal and hindlimb resistance vessels. With kidney and hindlimb perfused at constant pressure a decrease in pressure in the carotid sinuses from 250 to 40-45 mm Hg (1 mm Hg = 133 N/m2) caused the respective blood flows to increase by 19 +/- 6% and 80 +/- 4% (mean +/- SE), and stimulating muscle receptors with capsaicin caused a further decrease of 49 +/- 9% and 4 +/- 2%, respectively. With perfusion at constant flow, the baroreflex caused an increase of 34 +/- 4 mm Hg in the renal perfusion pressure and of 99 +/- 10 mm Hg in the hindlimb; capsaicin caused further increases of 203 +/- 17 and 35 +/- 9 mm Hg; respectively. These responses were abolished by sympathectomy. Capsaicin injection increased mean renal sympathetic nerve activity by 111 +/- 16% over the maximal impulse frequency recorded when the carotid sinus pressure was 40-45 mm Hg. Thus, withdrawal of the restraint exerted by the carotid baroreceptors on the pool of central neurons controlling the vascular beds of the hindlimb and kidney leads to near maximal constriction of the resistance vessels in the former bu not the latter; with strong activation of muscle receptors, near maximal constriction occurs in both beds.

Animals↗
PubMed1975

Effect of hypoxia on vascular responses to the carotid baroreflex.

The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.

Animals↗