Telemetered Renal Blood Pressure and Flow Responses to Situational Stress in Unrestrained Dogs

TELEMETERED RENAL R~~AL BLOOD PRESSURE AND FLOW RESPONSES TO SITUATIONAL STRESS IN UNRESTRAINED DOGS Christopher M. Stevens University of Southern California School of Medicine Department of Physiology Los Angeles, California 90033

Roland D. Rader University of Southern California School of Medicine Department of Physiology Los Angeles, California 90033

INTRODUCTION

the efferent arterioles in para parallel llel with the filtration and the absorption resistances form a second major resistive site. Downstream from the compliant peritubular capillaries the venules form a third resistive site. From this resistive site the flow channels join the interlobular veins. An component renal he~o~ynamic he~o~ynamic electronic model of the component parameters conceptualized by Rader et al. ,1) is illustrated at the top right in Figure 1. Pre- and postglomerular resist resistances ances and the compliance of the arteries preceding the afferent arterioles can be estimated on the basis of of the model by considerc onsidering the dynamics of recorded pressure and flow. calcula tions are summarized in the balance of These calculations the figure.

The development of a reliable method for assessing the perceived magnitude of a situational stress in dogs based upon observed changes in cardiovascular parameters is the thrust of this investigation. One aspect of this research has involved the conceptualization of a renal hemodynamic model which provides a method for determining instantaneous impedance changes in the kidney. By analysis of wave shape and amplitude of renal blood pressure and flow it is feasible to estimate vascular resist ance changes occurring in the kidney. resistance Furthermore, these impedance relationships provide an indication of change in renal hemodynamics which is more revealing than the overall pressure ow responses. and fl flow A second aspect of this research has involved the use of the renal model and totally implanted telemetry to measure renal responses. Both physiologica physiologicall and psychological factors can produce fluctuations in vascular tone. The sympathoadrenal system complex is responsive to a variety of environmental conditions, which, via alterrenal impedance, effect variations in ations in renal fluid and electrolyte balance. Thus superimposed upon the autoregulatory phenomenon in the kidney lies a neural-endocrine control mechanism. There a re indications that control of preglomerular are resistance may be primarily neural, whereas, the postglomerular resistance is mediated by hormones. The application of implanted telemetry for chronica lly monitoring systemic blood pressure and ically renal flow permits the quantification of hemorenal dynamic components of the renal vascular bed in unrestrained dogs. It is proposed that these component values might then be used as indices of renal function, levels of of autonomic arousal, and possibly level and location of renal atherosclerosis. Furthermore, because of the apparently differing effects neurogenic and hormonal hormona l influences have on the component values, an assessment of the relative contribution of the neurogenic and hormonal factors operating in a given situati on may be made. tion HEl40DYNAMIC MODEL RENAL HEHODYNAMIC Blood flow in the kidney is through multiple individual channels that are similar in anatomical arrangement but vary in diameter, length, wall thickness, and in the relative amount of collagen and elastin. The first primary resistance site is encountered at the afferent arterioles where it is contiguous with the compliant glomerular capillaries. On the exit side of the glomerular capillaries, but preceding the peritubular capillaries,

From the model glomerular filtration rate (GFR) for one kidney can be defined as GFR

Pg - Pp Rg + Rp

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involved the characterization of the normal renal hemodynamic responses of the dog to a variety of environmentally and experimentally induced situations. To date spontaneous 24-hour activity, acute territorial intrusion, isolation, and denial of accustomed activities, and obedience training have been employed as situational stresses while their effects upon renal hemodynamics have been monitored. In addition, the effects of acetylcholine and angiotensin upon the component resistance values were examined using exogenous acetylcholine chloride and angiotensin amide. Figure 2 illustrates responses obtained from a dog that was instrumented with implantable pressure and flow sensors coupled with an externally located acquisition acquisiti on system. This experimental sequence was performed to t o demonstrate demonstra t e the t he relative r el a tive effects of acetylcholine the~re- and of acetylcholi ne aand nd angiotensin angi otensin upon the~repostglomerular resistance sites and thus Pg and a nd GFR. The character char a ct er of the flow f l ow when the t he effects of pentobarbital of pent obarbita l are likely the most influential, i nfluenti al, i.e. the far left and a nd far f a r right column c olumn of the t he figure, is consistent with wit h the sympathomimetic sympa thomi metic effect of pent pentobarbital. obarbital. The altered character of the fl flow ow in the case when the effects of angiotensin are added to the pentobarbital is produced by even greater vasoconstriction. The wave shape in this case is quite close to the wave shape of the pressure, indicating a very rigid renal vascular system. Flow wave shapes resulting from constricted vessels can be contrasted with the wave shape generated when acetylcholine is the dominant pharmacologic agent. In this case, pressure and flow are both decreased fr from om control contr ol values. The afferent resistance is decreased and the post glomerular resistance is elevated. The decrease in the afferent resistance is likely due to the direct effect of acetylcholine upon the smooth muscle and possibly to cholinergic neurQdilatory effects on the kidney. The postglomerular resistance increase appears to be an attempt to maintain a normal filtration filtratio n pressure and a nd GFR in t he face of a declining blood pressure. It appears the from the calculati calculations ons based upon the model that the postglomerular resistance increase actually overcompensates for the decrease in Pi. This disparity between pre- and postglomerular resistances and the relationship of the renal response to the ~o~e ~o~e level of acetylcholine was observed by Vander (4). He found that high doses produced a i ncrease in renal plasma flow than t han did smaller increase moderate doses. moderate Figure 3 illustrates responses obtained from a dog i ns tr umented with an a n implantable t hat ,res fully instrumented that a nd flow telemetry system. s ystem. This experipressure and mental sequence was designed to induce progresstimuLa t~on from sively increasing autonomic stimuLat~on control through avoidance behavior. In this case, avoidance behavior was defined as the animal's reaction to the prospect of having the implant site touched. As the psychosocial stimulation increased, the pressure increased and the values calculated for all resistances increased. However, nor the neither the value of the total resistance nor post glomerular to total resistance ratio of postglomerular changed sufficiently to prevent an increase in total renal flow or an increase in the glomerular filtration pressure. As compared to the control value, the compliance decreased for the obedience

training and avoidance episodes. The increase in compliance from obedience training to avoidance may be associated with expansion of the vessels preceding the afferent resistance site by the inordinately high pressure. Here again,as was the case in the angiotensin administration, the increase in Pg and GFR appears to come as a result of the elevated perfusion pressure. ACKNOWLEDGEMENT This work was supported by the United States Air Force Office of Scientific Research Grant No. AFOSR-72-2190. REFERENCES (1)

Rader, R. D., C. M. Stevens, J. P. Henry, and J. P. Meehan, "Use of Implanted Telemetry in Vascular Research," Proceedings Pr oceedings of the 1 2 International Telemeterin Conference, Los Angeles, Calif. Oct 10-12 10 -12 , 8:4878: 487- 498, 98 , 1972.

(2)

Gomez, D. H., t4., "Evaluation of Renal Resistances, With Special Reference Refere nce to Changes in Essential Hypertension," J Clin Cl in Invest 30:1143-1155, 1951.

(3)

Brenner, B. M., J. L. Troy, T. M. Daugharty, Daughart y , W.. M. Deen, and C. R. Robertson, "Dynamics of W of Glomerular Ultrafiltration in the Rat. II. Plasma-Flow Dependence of GFR," 11. Am J Physiol 223(5):1184-1190, 223( 5):1184-1190, 1972.

((4) 4)

of Acetylcholine, Vander, A. J., "Effects of Atropine, and Physostigmine on Renal Function in the Dog," Am J Physiol Physi ol 206(3):492-498, 206(3):492-498 , 1964.

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