Citations

In closed-chest atropinized dogs anesthetized with chloralose and ventilated artificially, the aortic nerves were cut beneath the nodose ganglion, and the carotid sinuses were either denervated or vascularly isolated and maintained at a pressure of 40 mm Hg. Denervation was established by the failure of the pressoreceptor systems to respond to mechanical stimulation. Cold block or section of the cervical vagi resulted in statistically significant increases in arterial blood pressure (18%), heart rate (3%), central venous pressure (13%), hind-limb perfusion pressure (12%), pressure within the occluded spleen (18%), and efferent renal sympathetic nerve activity (28%). There was no change in saphenous vein perfusion pressure. The vascular responses were abolished by a-receptor blockade and were not affected by section of the vagi at the diaphragm. When the pressure in the vascularly isolated innervated carotid sinuses was varied from 40 to 220 mm Hg, the vascular responses to vagal block decreased steeply between 100 and 160 mm Hg and were absent at 200 mm Hg. Thus, receptors in the cardiopulmonary region with afferent vagal fibers exert a continuous restraint on the sympathetic adrenergic outflow to resistance and capacitance vessels, especially when the input from the carotid baroreceptors is decreased.

Microspheres of different sizes, 125 I-labeled antipyrine (I-Ap), and 42 KCl or 86 RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g -1 . After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of 42 K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of 42 K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15-30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or 42 K.

The effect of stimulation of somatic afferents from muscle was investigated in 24 anesthetized dogs. The carotid sinuses were isolated and kept at constant pressure, the vagi were cut, and the left iliac artery was isolated and perfused at constant flow. Muscle afferents were stimulated by either inserting electrodes into the muscles of the right thigh or stimulating the central end of the right femoral nerve. Muscle stimulation at 5 Hz decreased perfusion pressure in the iliac artery 76 ± 6 mm Hg (mean ± SE ); the decrease was not prevented by paralysis of the stimulated muscles, administration of atropine or antihistamines, or -receptor blockade. Muscle stimulation at 40 Hz increased perfusion pressure in the iliac artery 28 ± 3 mm Hg. This increase was prevented or changed to a depressor response by muscle paralysis. Similar effects were obtained with femoral nerve stimulation. Both depressor and pressor responses persisted after the leg had been skinned and the muscles had been separated from their tendons, but they were abolished by left sympathectomy. Thus, skeletal muscle contraction is necessary for activation of the muscle afferents which cause reflex vasoconstriction but not for activation of those which cause reflex vasodilatation.

Depressed myocardial contractility with paradoxically increased oxygen consumption has been demonstrated in previous studies of pressure overload hypertrophy. To determine whether altered mitochondrial respiration participates in the abnormal energetics of this muscle, right ventricular hypertrophy (RVH) was produced in 12 cats by pulmonary artery banding. A polarographic muscle bath was used to study eight control and eight RVH papillary muscles, and the respiration of mitochondria isolated from these right ventricles was characterized. RVH muscles demonstrated depressed force-velocity and length-tension curves. The myocardial oxygen consumption per gram of peak active tension was increased from 0.65 ± 0.05 nliters/mg beat -1 (control) to 1.10±0.07 nliters/mg beat -1 (RVH) ( P <0.001). Abnormal mitochondrial respiration was shown by an increase in the rate of state 4 oxygen consumption from 12.5±0.8 natoms/mg min -1 (control) to 19.9±0.8 natoms/mg min -1 (RVH) ( P < 0.001). The altered oxygen cost of active isometric tension in the RVH muscles was linearly correlated with the altered rate of mitochondrial state 4 oxygen consumption ( r = 0.91). Ruthenium red, a compound that blocks mitochondrial calcium uptake, reduced the rate of RVH state 4 oxygen consumption to the control level. The present study suggests a mechanism for the abnormal myocardial oxygen consumption in pressure overload hypertrophy and relates it to nonphosphorylating mitochondrial respiration linked to calcium transport.

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.

The vascular effects of graded stimulation of the carotid chemoreceptors were studied in 13 anesthetized and artificially ventilated dogs, and stimulus-response curves were defined. The carotid bifurcations were isolated and perfused at constant pressure, and the vagi were cut. Autologous blood collected in a reservoir was equilibrated at Po 2 varying from 104 to 34 mm Hg, Pco 2 from 39 to 81 mm Hg, and pH from 7.46 to 6.87 and was used to stimulate the carotid chemoreceptors. Systemic arterial Po 2 , Pco 2 , and pH were kept normal. Reflex increases in aortic blood pressure and in hind-limb perfusion pressure (constant-flow perfusion) were first seen with Po 2 of 70 mm Hg or Pco 2 > 39 mm Hg. The vascular responses increased linearly with lower Po 2 or higher Pco 2 , until tensions of 34 and 71 mm Hg, respectively, were reached. These stimuli caused a reflex dilatation of the perfused saphenous vein that was also proportional to the degree of stimulation. Increasing the pH of the blood perfusing the chemoreceptors decreased these changes by more than 50%; decreases in pH, with normal Po 2 and Pco 2 , caused marked vascular responses, indicating an important role of pH in the activation of the chemoreflex mechanism.