SUMMARY The prolonged effects (42 days) of indomethacin treatment on the renin-angiotensinaldosterone axis, renal hemodynamics, and renal excretory function in humans were studied. Indomethacin produced a 41% sustained depression in the 24-hour excretion of prostaglandin E 2 and a mild (7%) decrease in inulin clearance but did not affect the clearance of p-aminohippurate, the 24-hour excretion of sodium and potassium, or the basal values of plasma aldosterone; however, it decreased the basal values of renin and prevented the stimulated (3 hours of walking) responses of plasma renin activity and plasma aldosterone. Indomethacin also produced a decrease in both the diuretic and saluretic response to furosemide and in the renal ability to concentrate urine. The indomethacin-induced hyporeninism and hypoaldosteronism were more pronounced when the subjects were receiving a sodium-restricted diet. This finding indicates that prolonged administration of anti-inflammatory drugs induces chronic hyporeninism and hypoaldosteronism. Prolonged treatment with indomethacin also produced some of the symptoms of a syndrome of hypoprostaglandinism, such as decreased plasma renin activity, plasma aldosterone, and urinary prostaglandin E 2 in association with increases in plasma potassium levels and diastolic pressure. (Hypertension 8: 677-684, 1986) KEY WORDS * renin • aldosterone • prostaglandin E 2 • furosemide • degenerative joint disease * low sodium diet R ENAL prostaglandins play an important role in mediating the release of renin 1 2 and in regu-. lating renal function, as estimated through changes in renal blood flow, M glomerular filtration rate, 7 and renal handling of sodium and water. 8 Evidence also indicates that prostaglandins have a renal protective effect, especially in situations characterized by a decrease of renal perfusion.9 " 1 ' Under normal conditions, however, blockade of prostaglandin synthesis in association with the short-term administration of nonsteroidal anti-inflammatory drugs decreases renin release without inducing a marked impairment in renal From the Department of Nephrology (L.M. Ruilope, J.M. Alcazar, E. Miravalles, and J. Rodicio), Hospital "1° de Octubre," and the Department of Endocrinology

SUMMARY In a group of six patients diagnosed as having unilateral renovascular hypertension due to fibromuscular dysplasia, inulin glomerular filtration rate, (GFR) and PAH renal plasma flow, (RPF) clearances, urine flow (V), urine sodium (UV Nl ), potassium (UV K ), urinary excretion of prostaglandin E^ (UV reEj ), thromboxane B 2 (UV TxJ , 2 ), and 6-keto prostaglandin F la (UV^^) were measured in each kidney before and after the i.v. administration of furosemide (20 mg). The basal values of GFR, RPF, UV Ni , UVpc E ,, UV TlB ,, and UV 6 . krto . PCFla were lower (p < 0.01) in the stenotic kidney. Furosemide increased RPF 11 % and 50%, GFR 25% and 62%, and V 142% and 280% in the contralateral and stenotic kidney respectively. The increase of UV Na was similar in the two kidneys. In the stenotic kidney, both UVpcEj and UVj^^pcf^ increased significantly (p < 0.01) with furosemide while UV TlB , remained unchanged. Furosemide did not alter the rate of excretion of the three prostaglandins measured in the contralateral kidney. We conclude that furosemide significantly improves renal circulatory and excretory function of the stenotic kidney. Since prostaglandin excretions also increased, the vasodilatation in the stenotic kidney may be prostaglandin mediated. IT is known that the vasodilator action of furosemide in the normal kidney is mostly mediated by increased synthesis of prostaglandins, 1 " 4 which may also modulate the diuretic effects of furosemide. 4 Furosemide is currently used in patients with unilateral renovascular stenosis; however, it is not known whether its hemodynamic and diuretic effects are equally exerted or predominantly exerted in the stenotic kidney or in the contralateral kidney. Further, we have no knowledge about the changes induced by furosemide in prostaglandin synthesis in the stenotic and contralateral kidney. 56 In a recent survey of the literature, 7 there is convincing evidence supporting the notion that increased synthesis of prostaglandins is important inFrom the Departments of Nephrology and Endocrinology, 1st October and Ramon y Cajal Hospitals, Madrid, Spain, and from the Departments of Nephrology and Physiology, Mayo Clinic and Foundation, Rochester, Minnesota.Supported by Grant HL16496 from the National Institutes of Health, the National Heart, Lung and Blood Institute, and grants from the Mayo Foundation and the Spanish Ministry of Health (FIS Exp. 83/0575).Address for reprints: Dr. J.C. Romero, Department of Physiology, 9th Floor Guggenheim Building, Mayo Foundation, Rochester, Minnesota 55905. the maintenance of renal blood flow during the early phases of renovascular hypertension. However, in the chronic stages of hypertension, the role of prostaglandins has not been adequately explored. 7This study was undertaken to determine the effect of furosemide on renal hemodynamics, renal excretory function, and postaglandin excretion in both the stenotic apd contralateral kidneys of patients with renovascular hypertension. Materials and Methods Patient ProtocolThe study was co...

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SUMMARY Strong evidence indicates that a high protein diet accelerates end-stage renal disease by increasing glomerular capillary pressure subsequent to renal vasodilatation. The mechanisms underlying this vasodilatation remain undefined, but they have been suspected to be mediated by a pituitary factor. To test this possibility, we measured changes in renal plasma flow and glomerular filtration rate induced by an intravenous infusion of a solution of amino acids in two patients with panhypopituitarism. These patients exhibited changes in renal hemodynamics comparable to those recorded in nine healthy volunteers. The results do not support involvement of the pituitary gland in the acute renal response to amino acids. 1 " 4 This phenomenon is of clinical importance because glomerular hyperperfusion subsequent to afferent arteriolar vasodilatation has been postulated to accelerate end-stage renal disease, 1 ' 2 whereas a low protein diet slows the progression of chronic renal failure.1 " 3 The mechanisms underlying the renal vasodilatation induced by a high protein intake are unknown, '• 2 although a slow, progressive vasodilatation has also been induced by intravenous infusion of an amino acid combination used for parenteral nutrition.5 " 7 Shortterm protein load or amino acid infusions have been suggested to be reliable indicators of renal functional reserve. 8 Because of these delayed renal responses, the renal effects of amino acids are not thought to be exerted directly. The preventive influence that hypophysectomy has on the effect of a high protein intake on renal hemodynamics in rats 9 has led to consideration of the hypothesis that the renal vasodilatation is mediated by a humoral mechanism(s) of pituitary origin. This study evaluated the effect of amino acid infusions in two men who had panhypopituitarism secondary to surgical ablation of hypophyseal adenomas. Patients and MethodsOne patient (Patient 1), a 39-year-old man, was evaluated for headaches and severe visual disturbances. Investigation disclosed a pituitary mass with suprasellar extension; however, pituitary function was normal. The other patient (Patient 2), a 40-year-old man, was initially evaluated for hypogonadism, and subsequently hyperprolactinemia (399 ng/ml) with a low serum testosterone value (40 ng/dl) was diagnosed. In both patients, surgical removal of the pituitary adenoma was successfully completed, and substitutional therapy (hydrocortisone, 30 mg/day, and thyroxine, 100 /i.g/day) was initiated 3 months postoperatively.The efficacy of the surgical procedure was checked before the amino acid infusion with standard endocrine tests in the absence of substitutional therapy for 2 weeks. The tests, performed 8 and 12 months postoperatively, revealed the following data. The serum levels of growth hormone failed to increase (values remained < 0 . 6 ng/ml) after insulin-induced hypoglycemia. The serum levels of cortisol ranged from 1.3 to 3.1 ng/dl; this finding confirmed the absence of pituitary adrenocorticotropic hormone reserve. A

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