Abnormalities of Renal Perfusion and the Renal System in Dogs with Chronic Aortic Coarctation

To clarify the role of the renin-angiotensin system in coarctation hypertension, 2-year-old inbred dogs with chronic neonatally induced thoracic aortic coarctation were subjected to 6 days of rigorous salt restriction. The following parameters were then measured: glomerular filtration rate, renal plasma flow, plasma renin activity, plasma renin concentration, renin reactivity, and renin substrate concentration. Glomerular filtration rate and renal plasma flow were significantly lower in salt-restricted coarcted dogs: 3.0 ± 0.2 and 9.0 ± 1.5 ml/min kg", respectively, compared with values of 4.0 ± 0.2 (P < 0.005) and 13.2 ± 0.9 (P < 0.025) ml/min kg" in salt-restricted controls. Plasma renin activity was abnormally high in experimental dogs: 13.5 ± 2.5 vs. 4.5 ± 1.5 ng angiotensin I/ml hour" in controls (P < 0.005). In addition, a significant elevation of renin reactivity (indicating a relative increase in circulating accelerators or a relative decrease in inhibitors of the renin reaction) was apparent in the plasma of coarcted dogs. Plasma renin concentration was elevated but to an insignificant degree in coarcted dogs, and renin substrate concentration was comparable with that of controls. The impaired renal perfusion and abnormal elevation of plasma renin activity during salt restriction is analogous to clinical and experimental observations in hypertensive states associated with total renal underperfusion and supports a major role for the renal pressor system in the pathogenesis of coarctation hypertension. The insignificant elevation of plasma renin concentration is not incompatible with this view. The demonstration of increased renin reactivity in coarctation hypertension provides additional evidence that acceleration of the renin reaction is common to all hypertensive states. • Despite extensive investigation, the pathogenesis of hypertension in aortic coarctation has not been clearly defined. The participation of a renal factor was documented in early studies (1, 2), but subsequent attempts to demonstrate decreased renal perfusion (3-6) or increased plasma renin activity (7-9) have been generally unsuccessful. Importantly, these studies were performed during unrestricted sodium intake. Recent reports suggest that, in hypertensive states characterized by reduced blood supply to the entire kidney mass (total renal underperfusion), depletion of extracellular volume may be necessary to unmask an abnormality in peripheral plasma renin activity (10, 11). Although aortic coarctation is potentially a state of total renal underperfusion, there has been no systematic application of From the Departments of Medicine and Surgery, the Veterans Admin-stration Hospital and the University of Oregon Medical School, Portland, Oregon 97207. This study was supported in part by the Portland Veterans Administration Hospital Research Committee and the Oregon Heart Association. Dr. Bagby is a Fellow of the Oregon Heart Association; Dr. McDonald, Dr. Po ter, and Dr. Bennett are supported by Portland VAH Grants MRIS 5577, MRIS 7140, and MRIS 0901, respectively. Received April 28, 1975. Accepted for publication August 12, 1975. Circulation Research, Vol. 37, November 1975 sodium depletion in this setting. Accordingly, our first objective was to determine the response of the renin-angiotensin system to sodium restriction in dogs with neonatally induced chronic aortic coarctation. Although the conventional measurement of plasma renin activity is often assumed to reflect only plasma renin concentration, other components of the renin reaction may independently influence this value (12). These components include renin substrate concentration and "renin reactivity," a measure of inhibitors or accelerators of the renin reaction. Accelerating factors (or the lack of inhibitors) producing an increase in renin reactivity have been observed in a variety of primary and secondary hypertensive states (12-16) and thus far appear to be common to all forms of hypertension studied. Our second objective was to examine these components of the renin reaction in coarctation hypertension, to assess their contribution to the conventional plasma renin activity, and to seek further insight into the pathophysiological significance of the in vitro renin reactivity measurement in hypertensive states.