Renin release was studied during the infusion of catecholamines (.7–5.6 µg/min) and angiotensin II (.25–1.05 µg/min) into the renal artery, and also during and following iv infusion of 16 µg/min noradrenaline. Filtration rate (Ccr), RPF, and RBF were estimated from the renal clearance of creatinine and the extraction ratio. Marked increases in renal vein renin titer and V-A renin difference occurred within 1 min of the onset of infusion of catecholamine into the renal artery and continued for 15 min beyond the infusion period. This infusion was always accompanied by diminished renal function. During iv infusion of noradrenaline, renin release did not usually occur, but on stopping the iv infusion, the ensuing fall in blood pressure was coincident with a marked release of renin apparently unaccompanied by decreased renal function. Infusion of angiotensin into the renal artery, in spite of causing renal vasoconstriction and marked decrease in urine volume, was not accompanied by renin release. The difficulties of measuring renin release under these conditions are discussed.

A B S T R A C T This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured.Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of "metabolic clearance." In addition, the "plasma production rate" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects.It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreased metabolic clearance, and (c) increased production of plasma cyclic AMP.

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It has been shown that nephrectomized animals, in general, are more reactive to angiotensin and renin than are control animals ( 1,2 ) . Potentiation of the responses has been noted not to appear until some hours postnephrectomy ( 3 -5 ) . Also, lower base line blood pressures have been noted in nephrectomized rats some hours postnephrectomy ( 5 ) .Pressor responses in dogs have been shown to be somewhat related to serum K levels. For instance, insulin administration to lower serum K in normal dogs decreased pressor responsiveness. The insulin effects were reversed by KCl administration. A corollary was the finding that hypokalemia induced by peritoneal dialysis in a nephrectomized dog decreased vascular responsiveness to pressors. Nephrectomized dogs with hyperkalemia showed increased responsiveness to pressors In view of the above findings, studies were undertaken to determine if there was any correlation between pressor responsiveness and serum K changes in bilaterally ureterally ligated or nephrectomized rats at a time postoperatively when the experimental groups showed increased sensitivity to intravenous angiotensin injections.Method. The rats used for the following experiments were males and weighed 2 80-3 80 g. The rats were designated as follows: M = mock operated, N = bilateral nephrectomy and UL = bilateral ureteral ligation. All operations were carried out using ether anesthesia. The mock operation consisted of exposing both kidneys by retroperitoneal incisions followed by appropriate suturing. In addition, some M rats were etherized but not operated. All animals were kept fasting after the operative procedures until the time of the (6)-sensitivity experiments or until measurement of serum Na and K.At the time of the sensitivity experiments (2-20 hr postoperatively), the rats were anesthetized with Nembutal ( 3 3 mg/kg). The blood pressure was obtained from the carotid artery via pressure transducer recording on a Grass polygraph. The jugular vein was used for the site of injections. The injections consisted of saline followed by different doses of angiotensin I1 followed again by injections of saline. The peak pressure responses were measured. The responses to saline injection alone, if any, were then subtracted from the responses to angiotensin 11.The plasma ion studires were carried out separately from the sensitivity studies on different groups of animals but the operative manipulations were the same as those used for the rats in the sensitivity experiments. There were 5 rats used in each group at different hours postoperatively. Plasma Na and K were measured by standard flame photometry techniques.The angiotensins used in these experiments were: (a) naturally occurring hog angiotensin II,l and (b) synthetic angiotensin I1 amide (5-valyl aspartyl amide angiotensin 11) purchased from Ciba.