Upsala J Med Sci 81: 109-1 1 1 , 1976 Influence of Sympathetic Nerve Activity on Renal Haemodynamics and Release of Renin A Preliminary Communication L.-E. LORELIUS, P.-0. LOFROTH, L. WIKLUND, C. MORLIN and H. &ERG From the Departments of Diagnostic Radiology, Radiophysics, Anaesthesiology, and Internal Medicine, University Hospital, Uppsala, Sweden Al3 S TRACT The role of the sympathetic nerve system is still unknown in different types of hypertension. The procedure used in the evaluation of suspect renovascular hypertension has been revised in such a way that renal blood flow, renal arterial blood pressure and plasma renin activity in renal vein could be determined prior to and after splanchnic blockade. A new devic-videovolumeter-has been used to investigate the blood flow. Some preliminary data are given. INTRODUCTION The significance of the sympathetic nerve system in different types of hypertension is still obscure in many respects (5). It is known, however, that this nerve system is one of several mechanisms in- volved in the regulation of renin release (4, 9). Renin has attracted considerable interest in recent years in association with hypertension, not only the secondary but also the primary form (2), and con- sequently increasing research has been devoted to the role of the sympathetic nerve system in these conditions. As the kidney plays a central part not only with regard to renin but also concerning other, partly unknown, circulation-regulating substances, it would be of value to gain more knowledge on the effect of sympathetic impulses on the haemodyna- mics of the kidney and on renin release. In the autumn of 1975 an investigation on these problems was begun, with the use of partly new methods. A preliminary report of the initial results is pre- sented in this paper. MATERIAL Six p a t i e n t s 4 men and 2 women-in the age range 36 to 63 years, with hypertension of suspected renal origin, have been investigated hitherto. The patients took no medication for at least 4 weeks prior to the investiga- tion, and for the last week of these 4 they stayed in hospital. For 5 days prior to the investigation a low- sodium diet was given ( c . 20 mmol Na+ per day) and also 40 mg furosemide (Lasixa) daily. This is the routine pro- cedure in our department in all investigations for suspect- ed renovascular hypertension (7). METHOD For investigating the effect of splanchnic blockade on the renal haemodynamics and renin release, we chose to make an extra study of the right kidney in addition to the routine investigation of both kidneys aimed a t revealing the presence of any significant renal arterial stenosis. The reason for this choice was that on the right side there is a greater distance between the kidney and the lung, which diminishes any possible influence of the lung on the '33Xenon measurement of the renal blood flow. A polyethylene catheter with an outer diameter of 18 gauche was inserted so that its tip lay at the level of the right anterior margin of the vertebral body L 1. This was done on the day before the investigation, so that the procedure should not affect the conduction capacity of the autonomous nerves and thereby the sympathetic flow to the kidney at the time of the investigation. The catheter was inserted under general anaesthesia, which was in- duced by 200-500 mg propanidid (Epontol"). On the morn- ing of the investigation day a catheter was inserted into the femoral vein by the Seldinger technique and advanced further. Blood samples were taken from the inferior vena cava and the left and right renal veins for renin deter- mination. This catheter was left in situ with its tip in the right renal vein for further sampling. A red Odman catheter with end-holes and no side-holes was then in- troduced through the contralateral femoral artery, also by the Seldinger technique. The pressures in the aorta and right renal artery were then recorded via the latter cathe- ter, using an E M T 34 pressure transducer (Siemens- Elema, Sweden). The renal blood flow was then meas- ured by videodensitometry, with selective injection of Upsala J Meed Sci 81 110 L.-E. Lorelius et ai. 8 ml AngiografV into the right renal artery under a pressure of 295 kPa. The results were analysed later by a videovolumeter (1). Selective arteriography was sub- sequently performed, with 12 ml Angiografin@, under a pressure of 295 kPa, and with an exposure frequency of three frames per s for 3 s, two frames per s for 2 s , one frame every other s for 6 s, or (in 2 cases) with cine-re- cording at 50 frames per s. The renal blood flow was then determined by selective injection 0.3-0.4 mCi lSXe into the right rend artery via the same catheter as mentioned above, which had been left in an unchanged position. Recordings were made over the kidney with a NaI scintillation spectrometer. The detector, which had a crystal diameter of 5 cm, was fixed in a cylindrical collimator with the anterior surface of the crystal lying about 8 cm from the margin of the collimator. The collimator was placed as close to the patient's skin as possible. The detector was placed on the ventral side of the patient, and was centred over the kidney under fluo- rescent control. The number of impulses that passed through the analyser was recorded in both analogue and digital form for subsequent analysis in a 2-compartment model. Further recordings of the blood pressure in the right renal artery were made, after which blood samples were again taken from the right renal vein for renin determina- tion. With the patient in the same position, splanchnic blockade was induced with 40 ml of 0.25% plain bupi- vacaine (Marcaine3 injected into the polyethylene catheter inserted on the previous day. The arterial blood pressure was recorded 10 and 20 min after induction of the blockade, and the renal blood flow was again determined by the Xenon method. Blood samples were also taken for renin determination. The patient, the collimator and the polyethylene catheter were kept in the same position throughout the examination. With the patient still in the same position, densitometry and angiography were repeated, after which the arterial blood pressure was recorded and blood samples were again taken from the right and left renal veins for renin determination. The investigation was completed with a left-sided renal angiography. The plasma renin activity was determined by a modified radioimmunoassay method (8). RESULTS After the induction of splanchnic blockade the mean blood pressure in the renal artery decreased by 15 to 20% in all assessable patients. This blood pressure reduction is of the same order of magni- tude as has been reported previously after splanch- nic blockade in patients without cardiovascular dis- orders (9). The total blood flow through the kidney, meas- ured with 133Xe, decreased in all patients. Our preliminary results indicate that there is good correspondence between blood flows measured densitometrically and those calculated from the 133Xe washout curve. Moreover, from the 3 patients for whom technically satisfactory 'curves were obtained by both methods of flow measure- ment, it seemed that flows measured from video- densitometric recordings over the areas in which the renal cortex dominates corresponded relatively well with the flows calculated from the most rapid component of the 133Xe curve. In 4 patients the blood flow through the renal cortex decreased after the blockade, while in one patient it increased. One patient was excluded from these results for technical reasons. After the blockade the vascular resistance in the investigated kidney was reduced in 3 patients, un- changed in 2 and somewhat increased in one (this latter patient had a vasovagal reaction). In the pa- tients with the highest mean arterial blood pressures the vascular resistance was reduced, while in those with more normal pressures it was less affected. Despite the decrease in blood pressure and in the total renal blood flow, an increased release of renin was not noted in any of the patients. DISCUSSION Renovascular hypertension is still, more than 40 years after Goldblatt's important discoveries, diffi- cult to understand in certain respects. By deter- mination of the plasma renin activity (PRA) in the renal veins, significant stenosis of the renal arteries can be revealed. More problematical, however, is the question of how, with a normal peripheral PRA, stenosis can give rise to hypertension ( 6 ) . The mechanisms of renin release have been part- ly established, but we still have relatively little knowledge about the interactions between them and their individual contributions to the total events. How great, for example, is the role of the sympa- thetic nerve system in comparison with that of the baroreceptor mechanism? Further, it is possible that the answer to this question might not be the same for individuals with healthy kidneys as for those with disorders of the kidneys and renal arteries. One of the aims of the present investiga- tion is t o elucidate the role of the sympathetic nerve system in renal arterial stenosis. This is only a preliminary report and is intended mainly as a methodological description. Some observed ten- dencies are of interest, however, and deserve some discussion. Despite the fact that the autonomous Upsala J Med Sci 81 Influence of Sympathetic nerve on renal haemodynamics 1 1 1 nerve blockade resulted in a reduced perfusion pressure in the kidney, PRA did not increase. The explanation for this must be that this blockade, which acts mainly upon the sympathetic nerves, eliminates the effect of a reduced renal arterial pressure. It is too soon to draw definite conclu- sions, as our investigation is only in its early stages. It would seem reasonable to propose, however, that the sympathetic nerve system plays a predominant role in the release of renin and perhaps over- shadows the effect mediated by baroreceptors in afferent renal arterioles. No absolute conclusions can yet be drawn as to differences in the behaviour of the sympathetic nerve system in kidneys with normal arteries and those with arterial stenosis. Another interesting finding is the relative reduc- tion in the cortical blood flow after the splanchnic blockade. Corresponding shunting, but in the other direction-from medulla to cortex-has been ob- served in dogs after stimulation of the renal nerves (3). Finally, it must be mentioned that none of the patients suffered any noteworthy discomfort from the investigation, even though it was somewhat longer than the selective renal vein catheterization, including nephroangiography, usually undertaken in these patients with renal arterial stenosis. No complications occurred in connection with the investigation, which was approved by the Ethical Committee of the Faculty of Medicine. REFERENCES 1 . Bjork, L., Erikson, U. & Hallstrom, A,: The video- volumeter. Upsala J Med Sci 79: 148, 1974. 2. Brunner, H. R., et al.: Essential hypertension: renin and aldosterone, heart attack and stroke. N Engl J Med286:441, 1972. 3. L a Grange, R. G., Sloop, C. H. & Schmid, H. E.: Selective stimulation of renal nerves in the anesthe- tized dog. Circ Res33: 704, 1973. 4. Michelakis, A. M. & McAllister, R. G.: The effect of chronic adrenergic receptor blockade on plasma renin activity in man. J Clin Endocrinol Metab 34:386, 1972. 5 . DeQuattro, V . & Miura, Y.: Neurogenic factors in human hypertension: Mechanism or myth? Am J Med 55: 362, 1973. 6. Schambelan, M., Glickman, M., Stockigt, J. R. & Biglieri, E . G.: Selective renal-vein renin sampling in hypertensive patients with segmental renal stenosis. N Engl J Med 290: 1153, 1974. 7. Strong, C. G., Hunt, J. C., Sheps, S. G., Tucker, R. M. & Bernatz, P. E.: Renal venous renin activity. Enhancement of sensitivity of lateralization by so- dium depletion. Am J Cardiol27: 602, 1971. 8. Wide, L.: Personal communication. 9. Wiklund, L.: Postoperative hepatic blood flow and its relation to systemic circulation and blood gases during splanchnic blockade and fentanyl analgesia. Acta Anaesthesiol Scand (Suppl.) 58: 5 , 1975. 10. Winer, N., Chokshi, D. S., Yoon, M. S. & Freedman, A. D.: Adrenergic receptor mediation of renin secre- tion. J Clin Endocrinol Metab 29: 1168, 1969. Received J a n u a r y 29, 1976 Address for reprints: Hans Aberg, M.D. Department of Internal Medicine University Hospital S-750 14 Uppsala Sweden Upsala J Med Sci 81