Suppressed Plasma Renin Activity in Adrenal Regeneration Hypertension KENKO HASATANI, SHINPEI MORIMOTO, AND RYOYU TAKEDA 2nd Department of Internal Medicine, School of Medicine, University of Kanazawa, Takara-Machi 13-1, Kanazawa City, Japan unilaterally nephrectomized rats with or without an enucleated adrenal, drinking saline. After furosemide administration, PRA significantly increased in the control rats drinking saline as well as in the unilaterally nephrectomized rats drinking tap water, with or without an enucleated adrenal, but the PRA values in these three groups were only half those of the control rats drinking tap water. An insignificant increase in PRA was found in unilaterally nephrectomized (±enucleation) rats drinking saline. These findings suggest that the lack of a PRA response in ARH may be due to the pronounced suppression of the juxtaglomerular cells caused by a high sodium intake and the reduction of the renal mass, independently of the corticosteroid(s) secreted by the enucleated adrenal. (Endocrinology 96: 1300, 1975)
ABSTRACT. To clarify the role of the enucleated adrenal in the suppression of plasma renin activity (PRA) in adrenal regeneration hypertension (ARH), PRA response to furosemide administration was compared at the 9th experimental week in three groups of rats, which had been subjected to (a) sham operation (control), (b) unilateral nephrectomy, (c) unilateral nephrectomy plus contralateral adrenal enucleation, and given on tap water or high sodium intakes. Urine volume and sodium, and changes in body weight and hematocrit, determined 90 min after administration of furosemide, did not show any significant differences among any of the experimental groups. The basal PRA was significantly decreased in rats of the other groups as compared to the control rats drinking tap water. A decrease in basal PRA was much more pronounced in the
I
N adrenal regeneration hypertension (ARH), the renin angiotensin system is suppressed as demonstrated by a decrease in plasma renin activity (PRA) (Morimoto et al., unpublished work), renal renin content (1) or juxtaglomerular granularity (2-4). Since procedures such as unilateral nephrectomy and a high sodium intake, each of which causes a decrease in PRA (5,6), have been customarily added to adrenal enucleation to induce ARH (7), it is not clear whether the mineralocorticoid(s) produced by the enucleated adrenal is responsible for the suppression of PRA. The present study was undertaken to clarify the role of the enucleated adrenal in the suppression of PRA. For this purpose, the PRA response to furosemide administration was compared in three groups of rats, subjected to (1) sham operation, (2) unilateral nephrectomy, (3) unilateral nephrectomy plus contralateral Received August 8, 1973. Supported in part by Grant 957100 from the Scientific Research Fund of the Ministry of Education of Japan. Address reprint requests to: S. Morimoto, 2nd Department of Internal Medicine, School of Medicine, University of Kanazawa, Kanazawa City, Japan.
adrenal enucleation, on both tap water and high sodium intakes.
Materials and Methods Female Wistar rats weighing approximately 70 g were used in this experiment. All of them underwent right unilateral adrenalectomy. The "adrenal enucleation" rats underwent unilateral nephrectomy (right), and the contralateral adrenal was enucleated by the technique of Ingle and Higgins (8). The "unilateral nephrectomy" rats underwent unilateral nephrectomy, and the contralateral adrenal was left intact. The "control" rats underwent exploration of the right kidney and left adrenal. Each group of experimental rats was further subdivided into two groups, one was given tap water and the other was given 1% saline to drink. The animals were fed on laboratory chow (Oriental K.K., Tokyo) and each group was kept in separate cages for 9 weeks. The blood pressure was measured at the end of the 9th week by plethysmogjaphy (Natsume-KN II type) without anesthesia. Thereafter, they were kept in uniform hydration as described by Aston (9). Under sodium pentobarbital anesthesia (50 mg/kg BW ip), 50 mg/kg BW of furosemide was injected into the left femoral vein. One ml of blood for PRA assay was drawn from the right femoral vein before and 90 minutes after the administration of furosemide. After the bladder was emptied, the urine was collected through the catheter
1300
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 15 November 2015. at 23:06 For personal use only. No other uses without permission. . All rights reserved.
1301
NOTES AND COMMENTS Base line
r P
ABSTRACT. To clarify the role of the enucleated adrenal in the suppression of plasma renin activity (PRA) in adrenal regeneration hypertension (ARH), PRA response to furosemide administration was compared at the 9th experimental week in three groups of rats, which had been subjected to (a) sham operation (control), (b) unilateral nephrectomy, (c) unilateral nephrectomy plus contralateral adrenal enucleation, and given on tap water or high sodium intakes. Urine volume and sodium, and changes in body weight and hematocrit, determined 90 min after administration of furosemide, did not show any significant differences among any of the experimental groups. The basal PRA was significantly decreased in rats of the other groups as compared to the control rats drinking tap water. A decrease in basal PRA was much more pronounced in the
I
N adrenal regeneration hypertension (ARH), the renin angiotensin system is suppressed as demonstrated by a decrease in plasma renin activity (PRA) (Morimoto et al., unpublished work), renal renin content (1) or juxtaglomerular granularity (2-4). Since procedures such as unilateral nephrectomy and a high sodium intake, each of which causes a decrease in PRA (5,6), have been customarily added to adrenal enucleation to induce ARH (7), it is not clear whether the mineralocorticoid(s) produced by the enucleated adrenal is responsible for the suppression of PRA. The present study was undertaken to clarify the role of the enucleated adrenal in the suppression of PRA. For this purpose, the PRA response to furosemide administration was compared in three groups of rats, subjected to (1) sham operation, (2) unilateral nephrectomy, (3) unilateral nephrectomy plus contralateral Received August 8, 1973. Supported in part by Grant 957100 from the Scientific Research Fund of the Ministry of Education of Japan. Address reprint requests to: S. Morimoto, 2nd Department of Internal Medicine, School of Medicine, University of Kanazawa, Kanazawa City, Japan.
adrenal enucleation, on both tap water and high sodium intakes.
Materials and Methods Female Wistar rats weighing approximately 70 g were used in this experiment. All of them underwent right unilateral adrenalectomy. The "adrenal enucleation" rats underwent unilateral nephrectomy (right), and the contralateral adrenal was enucleated by the technique of Ingle and Higgins (8). The "unilateral nephrectomy" rats underwent unilateral nephrectomy, and the contralateral adrenal was left intact. The "control" rats underwent exploration of the right kidney and left adrenal. Each group of experimental rats was further subdivided into two groups, one was given tap water and the other was given 1% saline to drink. The animals were fed on laboratory chow (Oriental K.K., Tokyo) and each group was kept in separate cages for 9 weeks. The blood pressure was measured at the end of the 9th week by plethysmogjaphy (Natsume-KN II type) without anesthesia. Thereafter, they were kept in uniform hydration as described by Aston (9). Under sodium pentobarbital anesthesia (50 mg/kg BW ip), 50 mg/kg BW of furosemide was injected into the left femoral vein. One ml of blood for PRA assay was drawn from the right femoral vein before and 90 minutes after the administration of furosemide. After the bladder was emptied, the urine was collected through the catheter
1300
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 15 November 2015. at 23:06 For personal use only. No other uses without permission. . All rights reserved.
1301
NOTES AND COMMENTS Base line
r P
