Shepherd, John T.

Changes in muscle and renal vascular resistances when the traffic in aortic or vagal nerves was interrupted were compared during normocapnia and hypercapnia in rabbits. The rabbits were anesthetized with sodium pentobarbital, paralyzed, and artificially ventilated; the sinus nerves were cut. A hind limb and a kidney were perfused at constant flow with autologous blood. With the vagi cut or cooled, blocking the aortic nerves by cooling caused a 49% and a 28% increase in limb and kidney perfusion pressures, respectively, during normocapnia (end-tidal CO 2 3-4%) and a 56% and a 69% increase during hypercapnia (end-tidal CO 2 8-10%). With the aortic nerves cut or cooled, vagal cold block increased the limb and kidney perfusion pressures 10% and 15%, respectively, during normocapnia and 17% and 61%, respectively, during hypercapnia. These responses were attenuated, especially in the kidney, when one of these pairs of nerves was intact (aortic nerve or vagus) and the other pair was blocked. Thus, hypercapnia augmented the vasodepressor reflexes from the aortic arch and the cardiopulmonary area. The effects of this phenomenon were greater on the renal vascular bed than they were on the muscle vascular bed.

Experiments were performed to determine whether acetylcholine affects the sympathetic activation of the cutaneous veins of the dog. Changes in isometric tension of saphenous vein strips were recorded at 37°C in an organ bath. Addition of acetylcholine at 10 -11 to 10 -8 g/ml did not affect basal tension, but larger doses (5 x 10 -8 to 5 x 10 -7 g/ml) caused a contraction of the strips which varied from slight to marked. Acetylcholine at 10 -8 to 10 -7 g/ml caused a further increase in tension when it was added to strips already contracted by norepinephrine, tyramine, KCl, or BaCl 2 ; in contrast, similar doses of acetylcholine caused relaxation of strips contracted by liberation of norepinephrine from the nerve terminals by electrical stimulation (1-10 cps). This relaxation was not influenced by propranolol or hexamethonium but was abolished by atropine (10 -8 g/ml). In intact dogs, the lateral saphenous vein was perfused with autologous blood at constant flow. A sustained venoconstriction was induced either by electrical stimulation of the lumbar sympathetic chain or by a continuous infusion of norepinephrine. An infusion of acetylcholine (10 -7 to 10 -6 g/ml min -1 ) relaxed veins constricted by sympathetic stimulation but not those constricted by norepinephrine. Thus, acetylcholine, in doses smaller than those known to have a direct constrictor effect, causes relaxation of cutaneous veins, probably by inhibiting the release of norepinephrine from nerve terminals.

Pressure-dependent changes in afferent activity in the aortic and the sinus nerves were studied in 17 anesthetized dogs that were artificially ventilated with oxygen. Systemic arterial blood pressure was varied either continuously or in steps over the range of mean aortic blood pressure from 220 to 50 mm Hg with a pressurized reservoir connected to the abdominal aorta. Multifiber preparations from 20 aortic and 8 sinus nerves were used, and stimulusresponse curves were defined by measuring the mean impulse frequency at the various levels of pressure. Heart rate and pulse pressure were similar during recordings from both nerves. The two curves were S-shaped, with that for the aortic nerve being to the right of that for the sinus nerve. The change in activity was approximately linear from 200 to 120 mm Hg (mean aortic blood pressure) in the aortic nerve and from 180 to 80 mm Hg in the sinus nerve; there was no significant change in impulse frequency below mean blood pressures of 100 and 70 mm Hg, respectively. The threshold systolic blood pressure was 95 ± 3 (SE) mm Hg for the aortic receptors and 62 ± 4 mm Hg for the carotid sinus receptors. Thus, in the dog, the aortic baroreceptors are involved mainly in the control of high blood pressure, whereas at lower pressures the major control occurs through the carotid sinus baroreflex.

Experiments were conducted in 35 anesthetized dogs to study the circulatory adjustments, after hemorrhage, mediated by vagal afferents from the cardiopulmonary area. With the aortic baroreceptors and chemoreceptors denervated and carotid baroreceptor and chemoreceptor activity held constant, hemorrhage of 10% of blood volume caused an increase in heart rate and constriction of the resistance vessels of the hindlimb, renal, and mesenteric beds and of the splanchnic venous bed. Vagotomy abolished these responses to hemorrhage, resulting in a greater decrease in blood pressure. With the carotid baroreflex operative, the constriction of the renal and mesenteric resistance vessels and of the splanchnic venous bed were similar to that obtained with only the vagi operative, but the constriction of the hindlimb resistance vessels was much greater and aortic pressure was better maintained. It is concluded that receptors in the cardiopulmonary area, subserved by vagal afferents, exert their main influence on the splanchnic resistance and capacitance vessels and on the renal circulation, whereas the carotid baroreceptors predominantly affect the muscle vessels.

The reflex cardiovascular response to stretch of left pulmonary vein-atrial junctions was studied in anesthetized dogs in which both aortic nerves were cut and the carotid sinuses were isolated vascularly. After thoracotomy, the root of the left lung was tied and a small Silastic balloon (1.5-cm long), attached to a nylon catheter, was inserted into each of the three left pulmonary veins and tied so that its tip lay at the junction of the vein with the left atrium. In six dogs, heart rate response to balloon distension of 2.0 ml was studied over a range of initial heart rates (75 to 240 beats/min) achieved by varying the carotid sinus pressure. On distension of the balloons, slowing occurred if the initial heart rate was > 140 to 150 beats/min and acceleration if it were less. In eight dogs, aortic blood pressure and cardiac output measured before, during, and after balloon distension (0.25 to 2.0 ml) demonstrated a hyperbolic relationship between balloon volume and decrease in calculated systemic vascular resistance. All responses were abolished by vagotomy. The reflex vasodilatation was sustained and caused by decreased adrenergic activity; the reflex bradycardia or tachycardia was due to interplay of vagal and sympathetic cardiac efferents.

Acetylstrophanthidin, 1.0 to 10.0 µg/ml, caused contraction of strips of the lateral saphenous vein of the dog in an organ bath at 37°C. The superior mesenteric vein, which exhibited spontaneous activity in the organ bath, responded to acetylstrophanthidin with an almost immediate increase in tension and an increased frequency of contractions; this was followed by a sustained contraction which had the same time lag as the contraction of a saphenous vein strip from the same dog. In strips from both veins, the contraction was depressed by cooling and augmented by warming, an effect opposite to that seen with norepinephrine-induced contractions. A latent period of 10 to 60 minutes preceded the contraction of the saphenous vein; during this time, the vein showed increased reactivity to added norepinephrine, 5-hydroxytryptamine, acetylcholine, barium chloride, increased bath concentration of K + , and decreased bath concentration of Na + . The increased reactivity and contraction still occurred after catecholamine depletion of the vein by chronic lumbar sympathectomy and in umbilical veins, which are devoid of adrenergic nerves. In addition to its direct constrictor action on cutaneous and mesenteric veins, acetylstrophanthidin sensitized cutaneous veins to vasoactive agents and to changes in ionic environment. These actions did not depend on the presence of norepinephrine in the veins.

It has been suggested that the pressor effect of hypertonic solutions of sodium chloride on the Pulmonary circulation results from spasm of the pulmonary veins at their junction with the left atrium. These studies demonstrate that the increased resistance in the pulmonary vessels develops upstream to this site and that it may result primarily from mechanical blockage of vessels by clumped erythrocytes rather than from vasoconstriction.