Prostaglandins may modulate renal function and play a role in the hyperreninism and angiotensin pressor resistance of chronic liver disease. To study this possibility, we evaluated 12 patients with alcoholic cirrhosis and ascites. Urine immunoassayable prostaglandin E in 5 female patients was 3.3 +/- 0.5 micrograms/day [normal, 0.3 +/- 0.1 (SE)], renin was 14.6 +/- 3.7 ng/ml.h, and aldosterone was 76 +/- 19 ng/dl. After either indomethacin (200 mg) or ibuprofen (2000 mg) for 1 day, urine immunoassayable prostaglandin E fell to 0.8 +/- 0.4 micrograms/day, renin to 8.0 +/- 2.4 ng/mol.h, and aldosterone to 54 +/- 14 ng/dl (all P less than 0.01). Pressor sensitivity increased dramatically, and creatinine clearance transiently fell from 73 +/- 10 to 32 +/- 7 cc/min (P less than 0.01). Because a primary effect on renin might explain the renal impairment, an additional study used propranolol to lower renin activity. Renal function was unaltered by propranolol. We conclude that prostaglandins play a supportive role in maintaining renal function and are involved in the hyperreninism and pressor resistance of patients with liver disease.

No abstract

A screening procedure for adrenocortical insufficiency, utilizing (synthetic a 1-24 adrenocorticotropic hormone [ACTH] and a cortisol-binding globulin technique for serum cortisol, has been evaluated in normal subjects and in patients with primary and secondary adrenal insufficiency. Co-syntropin is injected by vein, and a serum cortisol concentration 60 minutes later is compared with a sample removed just prior to the cosyntropin administration. A clear separation of normal subjects from those with adrenal insufficiency is achieved.It is generally accepted that a single plasma cortisol or urinary steroid determination may not dis¬ tinguish adrenal insufficiency from normal adrenal function. Therefore, corticotropin stimulation is required to differentiate one from the other. A standard corticotropin stimulation test requires either a prolonged intra¬ venous infusion or repeated intra¬ muscular injections of corticotropin, along with frequent venipunctures or 24-hour urinary collections. This type of testing is time consuming and may necessitate hospitalization in order to obtain accurate results. A more rapid screening procedure for the detection of adrenal insufficiency which may be employed in either hospital or office is needed. The recent availability of a commercial form of synthetic adrenocorticotropic hormone (ACTH), com¬ bined with improved methods for de¬ termining plasma cortisol levels, has provided an opportunity for the de¬ velopment of an accurate, rapid, simple, and safe testing procedure for the detection of adrenocortical in¬ sufficiency.Shorter procedures for testing ad¬ renal reserve have been recently de¬ veloped and widely used in Europe.11 These methods have employed cosyntropin (synthetic a 1-24 ACTH) intramuscularly and have measured adrenocortical response by the use of a fluorometric cortisol determination.A similar procedure utilizing the plasma fluorescent cortisol response to the rapid intravenous adminis¬ tration of a commercial corticotropin extract has also been reported.4 Cosyntropin possesses low antigenic po¬ tency and can usually be employed safely in patients known to have al¬ lergies to ACTH extract.We describe a testing procedure which can be used for the assessment of adrenocortical response, employing a single intravenously administered dose of cosyntropin. Plasma cortisol has been measured by a competitive protein-binding assay method utiliz¬ ing cortisol-binding globulins (CBG).' This method, in our experience, is su¬ perior to the standard fluorometric cortisol technique in that it possesses greater sensitivity and reliability.6'8 It appears that a single intravenous dose of cosyntropin, when employed with the CBG method, fulfills the clin¬ ical requirements for a rapid, accu-rate, and simple screening test for the detection of adrenocortical in¬ sufficiency. Materials and Methods The adult study subjects were selected from the wards and clinics of the Los An¬ geles County-University of Southern Cal¬ ifornia Medical Center. Nine patients formed the control group. A del...

To investigate the possible interrelationship between the renin-angiotensin and prostaglandin systems, two groups of normal men were evaluated under conditions of varied sodium intake and after indomethacin, an inhibitor of prostaglandin synthesis. Eight subjects were placed on a 200 mEq Na diet and given 45 min infusions of prostaglandin A1 (PGA1) at 0.075 microng/kg/min and angiotensin II at 10 ng/kg/min on separate mornings. PGA1 produced a significant rise in both plasma renin activity (PRA) and aldosterone. Angiotensin II caused a similar rise in aldosterone. The patients were then placed on a 10-20 mEq Na diet and the infusions repeated. PGA1 again induced a further increase in both PRA and aldosterone. Angiotensin II produced the expected increase in aldosterone while PRA decreased. Body weight and 24 h sodium excretion were not different from control days on either diet. When indomethacin was administered to patients on the low sodium diet, PRA fell significantly and there was an increased pressor responsiveness to angiotensin. In a separate group of 4 patients on a low salt intake, basal PRA fell significantly during a 4 day period of indomethacin administration and returned to control values within 48 h after discontinuing the drug. These studies suggest that PGA1 infusions stimulate renin release independently of sodium balance. Inhibition of prostaglandin synthesis lowers PRA and increases pressor responsiveness to angiotensin. The data provide further evidence that vasodepressor prostaglandins may play a role in renin release and blood pressure homeostasis.