Sympathetic Vasomotor Outflow Research Articles

Location of the area postrema pressor pathway in the dog brain stem.

Electrical stimulation of the dog's area postrema (AP) induces a response that mimics the pressor response produced by intravertebral infusion of low-dose angiotensin II, which causes an increase in mean arterial pressure associated with transient tachycardia and increased peripheral resistance. The present study investigated in morphine-chloralose anesthetized dogs whether: 1) the characteristics of the AP pressor response are influenced by the presence of carotid sinus afferents; 2) structures rostral to the medulla influence the AP pressor response; and 3) the pressor pathway is initiated by neurons within the AP. Since bilateral cervical sinovagal denervation, which potentiated the phenylephrine pressor response, did not affect the pressor response to AP stimulation, the data provide evidence for an inhibitory influence exerted upon the central baroreflex mechanism by the AP pressor mechanism. The unaltered AP pressor response after midcollicular transection suggests that the efferent pathway is contained within the brain stem caudal to the pons. Finally, the elimination of the pressor response following kainic acid microinjection into the AP provides evidence that the AP pressor mechanism is initiated by neurons within the AP, rather than by fibers of passage from other pressor centers. These results suggest that the AP produces its facilitation of central sympathetic vasomotor outflow via a pathway contained within the medulla.

Plasma norepinephrine in the evaluation of baroreceptor function in humans.

The value of plasma norepinephrine measurement in assessing baroreceptor-mediated changes in sympathetic vasomotor activity was studied in seven healthy normotensive volunteers. Blood pressure was decreased by graded steady-state infusions of sodium nitroprusside (25-100 micrograms/min) and increased by infusions of phenylephrine (25-100 micrograms/min) at rates producing a 10% to 20% change in diastolic blood pressure. Sodium nitroprusside produced significant decreases in diastolic blood pressure (p less than 0.01) and calculated mean arterial blood pressure (p less than 0.005), and increases in heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.001). Phenylephrine administration produced increases in systolic (p less than 0.005), diastolic (p less than 0.005), and mean blood pressure (p less than 0.001). Heart rate (p less than 0.001) and plasma norepinephrine (p less than 0.05) fell. The absolute changes in diastolic and mean pressure and heart rate were not significantly different for the two drugs, but were of opposite sign; however, the increase in plasma norepinephrine during hypotension was greater than the decrease during hypertension (p = 0.02). We conclude that plasma norepinephrine changes appropriately in response to altered blood pressure and that the response is greater to a given fall than to a rise in blood pressure, consistent with known changes in sympathetic vasomotor outflow.

Angiotensin and CNS regulation of blood pressure.

It appears that angiotensin II (AII) has access to the CNS by three routes: endogenous formation within the brain, passage into CSF, or transfer across "gaps" in the blood-brain barrier. The mode of access influences both the characteristics and the magnitude of the cardiovascular effects exerted by AII within the CNS. In the dog the effects of blood-borne AII on the area postrema (AP) in the IV ventricle seem to have the most physiological significance. In recent experiments we have characterized both the histological composition of this structure and its physiological effects. While electrical stimulation of the AP, in similarity to the pressor effects of intravertebral AII, produces a hypertensive response dependent on sympathetic vasomotor outflow, ablation of this structure results in mild hypotension associated with decreased hemodynamic variability and altered vascular responsiveness to intravenous AII and norepinephrine. Recent data suggest that the sympatho-facilitative action of AII on the AP may involve endogenous opiates in the brainstem.

Brain Lesions and Hypertension: Chronic Lability and Elevation of Arterial Pressure Produced by Electrolytic Lesions and 6-Hydroxydopamine Treatment of Nucleus Tractus Solitarii (NTS) in Rat and Cat

This chapter attempts to produce experimental neurogenic-hypertension in laboratory animals by electrolytic and chemical lesions of the brain. It demonstrates that it is possible to produce chronic hypertension by lesions of nucleus of the tractus solitarii (NTS), thereby validating the hypothesis that central neural imbalances can result in hypertension. The chapter also presents the studies demonstrating that selective destruction of the noradrenergic innervation of NTS by the drug 6-hydroxydopamine (6-OHDA), which selectively destroys noradrenergic terminals, can result in the development of marked lability of the arterial pressure. This would suggest that the defects of chemical neurotransmission within the central nervous system (CNS) could possibly contribute to the conditions favoring the development of hypertension. It is concluded that chronic neurogenic hypertension can result from imbalances in the CNS that result in disinhibition of sympathetic vasomotor outflow. Specific biochemical defects of neurotransmitter systems, particularly of the noradrenergic innervation of the NTS, could possibly lead over time to the development of hypertension.

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.

Potentiation of hypothalamic pressor responses in awake rats treated with contraceptive steroids.

Contrasting with the hypertension resulting consistently after DOCA implantation, mature female rats given Enovid daily for 20 weeks had only slight and occasional increases in blood pressure. The pressure elevations remained infrequent and transient even when drinking water was replaced with isotonic saline solution but they became more pronounced when Enovid treatment was initiated at an earlier age. Despite the failure to cause sustained hypertension, the data indicate that Enovid affects blood pressure and that both mestranol and norethynodrel are essential for this effect. Pressor responses to norepinephrine or angiotensin were unaffected even after 20 weeks of pretreatment but those to electrical stimulation of the posterior hypothalamus were increased in rats pretreated with Enovid. Enhanced responsiveness to hypothalamic stimulation occurred only in the awake state and was not demonstratable after the central nervous system (CNS) had been depressed with urethane. These results can be explained by an increased sensitivity of hypothalamic pressor areas produced by Enovid prior to the development of hypertension and the mechanisms involved may be similar to those occurring in spontaneously-hypertensive rats. However, the possibility of hypersensitivity at other sites in the sympathetic vasomotor outflow cannot be ruled out.

Letter: Intestinal ischemia and digitalis.

To the Editor.— In his article, Recovery from Acute Intestinal Ischemia Without Bowel Resection (226:776, 1973), Dr. Vyden pointed out the importance of congestive heart failure in the pathogenesis of ischemic bowel disorder. He found the ischemic process to be reversible by appropriate treatment of the primary cause. In congestive failure, passive venous congestion to the splanchnic circulation and simultaneous increased sympathetic discharge result in vasoconstriction. The increase in sympathetic nervous outflow to the heart to increase rate is directly proportional to the increase in the sympathetic vasomotor outflow necessary to constrict visceral organs. 1 Thus, the tachycardia in failure may be an index to the degree of vasoconstriction in the splanchnic bed. Digitalis, by ameliorating cardiac performance and output, tends to lessen passive venous congestion and also reduce vasoconstriction through diminished sympathetic outflow. Both cases presented by Vyden were treated with digitalis. In case 2, digoxin was given prior

Periodicities in efferent discharge of splanchnic nerve of the cat.

Periodicities in efferent discharge of splanchnic nerve of the cat.

Relationships among intravascular volume, total body sodium, arterial pressure, and vasomotor tone.

In rats made hyponatremic, hypovolemic, and hypotensive by intraperitoneal injections of 5 per cent glucose solution, arterial pressure was returned to control values by correction of the intravascular-volume deficit with either 5 per cent salt-free albumin or small volumes of hypertonic sodium-chloride solution. In the former, severe hyponatremia persisted; in the latter, it was corrected. Isotonic sodium-chloride solution, given in amounts considered sufficient to repair the extracellular-fluid and electrolyte deficits, was not so effective either in controlling hypotension or in expanding the intravascular volume. Using the height of the norepinephrine pressor response and the duration of the serotonin depressor phase as estimates of sympathetic activity, sympathetic vasomotor tone was found to be enhanced during hyponatremic, hypovolemic hypotension and depressed by administration of 5 per cent albumin, hypertonic and isotonic sodium-chloride solutions. These changes in estimates of sympathetic activity seemed dependent on changes in intravascular volume and not in extracellular sodium concentrations. Experiments performed following pentolinium-induced ganglion blockade showed that the depressor phase of the serotonin response was dependent on sympathetic vasomotor outflow, but that the height of norepinephrine pressor response was dependent not only on sympathetic activity, but also on the intravascular volume. In this study of selective sodium deficit, intravascular volume was found to be an important determinant of arterial pressure and sympathetic vasomotor tone.