Vernon S. Bishop

Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits.

This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.

Permeability of the Alveolar Membrane to Solutes

The lower lobe of the left lung of 54 dogs was isolated and perfused with a dextran-Tyrodes solution. The alveoli were filled with Tyrodes solution, and permeability coefficients were measured for diffusion of several substances across the alveolar membrane. The permeability coefficients of the pulmonary membrane for K42, urea, Na24, glucose, D2O, and dinitrophenal(DNP) were 56.5 ± 3.5, 22.9±9.2, 7.5±2.1, 3.1±0.7, 400, and 400×10−7 cm/sec, respectively. The effect of varying the flow rate on the permeability coefficient of Na24 was investigated, and the data failed to show any significant correlation between the flow limits of 3.8 to 12. 8 cm/min/g lung tissue. The effect of two different procedures for filling the alveoli with fluid on the permeability coefficients was also investigated and no difference could be discerned in the results. The data support the thesis that the alveolar membrane has permeability characteristics similar to those of the usual cell membrane. The interstitial fluid volume of the lung (extravascular sodium space) was measured and yielded a value in normal lungs of 0.250 ± 0.129 cc/g lung tissiue. In three edematous lungs, this space averaged three times the normal value.

Spinal Sympathetic Cardiocardiac Reflexes

We studied the reflex changes in myocardial contractility elicited by electrical stimulation of afferent cardiac sympathetic nerve fibers or chemical stimulation of their cardiac endings. Veratridine injected directly into the left coronary artery was the chemical stimulus. The maximum rate of rise of left ventricular pressure, dP/dt max, was used as an index of myocardial contractility. The stimuli evoked increases in dP/dt max in vagotomized cats with or without spinal transection (C1). Electrical stimulation provoked the same effect in vagotomized dogs. Increases in dP/dt max occurred which were independent of changes in heart rate, preload, or afterload. They were reflex in nature since they were abolished by section of the upper thoracic sympathetic rami or cardiac sympathetic nerves. These results are the first demonstration of a cardiocardiac reflex which can be mediated entirely by the spinal cord. Electrical stimulation in vagotomized cats and dogs also produced a reflex increase in arterial blood pressure partly due to sympathetic vasoconstriction.

INTERACTIONS BETWEEN VASOPRESSIN AND BAROREFLEX CONTROL OF THE SYMPATHETIC NERVOUS SYSTEM

1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho‐inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho‐excitation to a decrease in pressure is reduced.

Involvement of the area postrema in the regulation of sympathetic outflow to the cardiovascular system.

The circumventricular organs of the brain have been implicated in the central regulation of the cardiovascular system. The area postrema, which is the only circumventricular organ in the hindbrain, has received less attention than the others, but recent studies suggest that it may play an important role in the regulation of the cardiovascular system. Studies in rats and rabbits indicate that angiotensin II (Ang II)-dependent hypertension is abolished by lesioning of the area postrema. Additional studies indicate that the hypertension associated with Ang II involves a resetting of the arterial baroreflex to a higher pressure. This upward resetting requires an interaction of neurons in the area postrema with barosensitive neurons terminating in the medial nucleus tractus solitarius (mNTS). Another peptide, arginine vasopressin (AVP), has been shown to enhance the sympathoinhibitory influence of the arterial baroreflex via an action at the area postrema. Studies in rabbits suggest that the sympathoinhibitory response is due to resetting of the baroreflex to a lower pressure. Electrophysiological studies, using an in vitro brain slice preparation, have shown that activation of area postrema neurons projecting to the mNTS alters the responsiveness of mNTS neurons to afferent inputs. It is postulated that alpha-adrenergic mechanisms are involved in these interactions.

Central Baroreflex Resetting as a Means of Increasing and Decreasing Sympathetic Outflow and Arterial Pressure

Abstract: The arterial baroreflex has two important functions. First, the arterial baroreflex is a negative feedback reflex that regulates arterial pressure around a preset value called a set or operating point. Second, the arterial baroreflex also establishes the prevailing systemic arterial pressure when the operating point is reset. That is, modulating the response of barosensitive neurons in the central nervous system (CNS) establishes the operating point or prevailing systemic arterial pressure. Therefore, the operating point of the arterial baroreflex is not fixed, but is variable over a wide range of pressures and is determined by a variety of inputs from the peripheral and central nervous systems. At the onset of dynamic exercise, heart rate (HR) and sympathetic nerve activity (SNA) increase abruptly and dramatically. The initial increase in HR and SNA is mediated by central command. Central command operates by resetting the operating point of the arterial baroreflex to a higher pressure. In this situation, the operating point of the arterial baroreflex is above the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by activating SNA and inhibiting parasympathetic nerve activity, which increases cardiac output and peripheral resistance and, consequently, arterial pressure. After exercise, loss of central command and enhanced activity of the cardiopulmonary reflex resets the operating point of the arterial baroreflex to a lower pressure. In this situation, the operating point of the arterial baroreflex is below the prevailing arterial pressure, which elicits a blood pressure error. This error is corrected by inhibiting SNA, which decreases peripheral resistance and consequently arterial pressure. In these situations, central resetting of the arterial baroreflex is a means of increasing and decreasing sympathetic outflow and arterial pressure.

Pregnancy attenuates activity of the baroreceptor reflex.

1. Pregnancy‐induced changes in acute blood pressure regulation are reviewed.

Influence of autoregulation and capacitance on diastolic coronary artery pressure-flow relationships in the dog.

We studied the influence of initial coronary artery pressure on pressure-flow relationships during long diastoles in 22 closed-chest, anesthetized dogs under basal conditions and after maximum coronary vasodilation. The circumflex artery was perfused from a pressurized arterial reservoir through a cannula inserted in the carotid artery. Diastolic pressure-flow relations were obtained under two conditions: (1) when pressure was gradually decreasing (40 mm Hg/sec); and (2) when pressure and flow were constant beginning 500 msec after a rapid step decrease in pressure. Pressure-flow curves obtained with pressure gradually decreasing were linear in the basal state and during maximum coronary vasodilation [r = 0.98 % 0.01 (SE)]. In autoregulating animals, 25 mm Hg increments in coronary artery pressure from 75 to 125 mm Hg resulted in progressive decreases in the slope (2.2 % 0.1 to 1.2 % 0.1 ml/min per 100 g per mm Hg, P < 0.01) and increases in the zero flow pressure intercept (37.3 % 1.4 to 51.2 % 2.1 mm Hg, P < 0.01) of the pressure-flow curves. These changes were not observed when autoregulation was abolished with intracoronary adenosine. Diastolic pressure-flow curves obtained under constant pressure conditions were also linear in the basal state and during maximum coronary vasodilation (r = 0.98 % 0.01). Increasing initial coronary artery pressure from 75 to 125 mm Hg resulted in a decrease in the slope (1.6 % 0.1 to 0.9 % 0.0 ml/ min per 100 g per mm Hg, P < 0.01) and an increase in the zero flow pressure intercept (21.1 % 2.1 to 37.2 % 2.3 mm Hg, P < 0.01) of the pressure-flow curves. With maximum coronary vasodilation, the slope increased to 4.7 % 0.1 ml/min per 100 g per mm Hg (P < 0.001) and the zero flow pressure intercept decreased to 15.2 % 0.7 mm Hg (P < 0.001). When pressure-flow curves obtained with pressure gradually decreasing were compared to ones obtained during constant pressure perfusion, the constant pressure values for slope averaged 10–25% lower (P < 0.01), whereas values for the zero flow pressure intercept were 8–12 mm Hg lower (P < 0.01). These data indicate that diastolic coronary artery pressure-flow relations obtained when pressure is continuously changing are influenced by coronary vascular capacitance. When capacitance effects were minimized, the slope and zero flow pressure intercept of the diastolic pressure-flow curves were dependent on coronary vasomotor tone, with the zero flow pressure intercept ranging from 15 to 37 mm Hg. These data are consistent with a vascular waterfall model of diastolic flow regulation. Based on such a model, we estimate that changes in coronary vascular resistance and zero flow pressure intercept can account for 70–80% and 20–30%, respectively, of the coronary autoregulation observed over the pressure range of 75 to 125 mm Hg.

Angiotensin Ii Modulation Of The Arterial Baroreflex: Role Of The Area Postrema

1. Resetting the operating point of the arterial baroreflex appears to be an important factor involved in determining the level of sympathetic outflow.

Stimulation of area postrema by vasopressin and angiotensin II modulates neuronal activity in the nucleus tractus solitarius

There is an abundance of evidence suggesting that the area postrema (AP) is involved in the central actions of arginine-vasopressin (AVP) and angiotensin II (Ang II) on cardiovascular regulation. Furthermore, recent studies have shown that activation of the AP facilitates the response of nucleus tractus solitarius (NTS) neurons to tractus stimulation. In the present study, using the perfused rabbit brain slice preparation, we examined the response of NTS neurons when AVP and Ang II were microinjected onto the AP. Spontaneous or solitary tract stimulation-induced neuronal activity was recorded extracellularly from the medial NTS before, during and after AVP or Ang II application. An increase or decrease in activity by more than 30% of the baseline value was considered excitatory or inhibitory. The effects of AVP were studied in 57 NTS cells, 14 of which were spontaneously active and 43 were driven by tract stimulation. Of the cells with evoked activity, 49% were excited, 19% were inhibited, and 32% did not respond. The percentage of cells responding to AVP was similar in spontaneously active cells. The effects of Ang II were tested in 85 cells including 54 with evoked activity and 31 with spontaneous activity. In NTS cells with evoked activity, AP application of Ang II caused inhibition in 37%, excitation in 7%, while 56% did not respond. The proportion of cells responding to Ang II was similar in spontaneously active cells. These results suggest that AVP may act on the AP to increase the excitatory response of NTS neurons while the actions of Ang II result in an inhibitory influence.