We investigated the effects of uraemia and haemodialysis on the basal activity of adenylate cyclase and the cyclic-AMP content of human platelets in patients with end-stage renal insufficiency, patients receiving maintenance haemodialysis, and as controls healthy voluntary subjects. Basal adenylate cyclase activity in terminal renal disease (creatinine clearance less than 15 ml/min/1.73 m2) was 824 +/- SEM 57, in comparison to the healthy subjects with 453 +/-SEM 28 (P less than 0.001). We also found significant elevation (P less than 0 . 001) of platelet cAMP levels as compared to the controls. Basal adenylate cyclase activity and platelet cAMP levels were approximately normal in the dialysed patients. These results show that uraemic toxins adversely affect the platelet AC-cAMP system, possibly causing impaired platelet aggregation and the bleeding diathesis of uraemia.

Clearance studies were made to determine the influence of intravenous infusions of dopamine (between 2.5 and 3.5 mug.kg.-1min.-1) on renal function and on the adenyl cyclase phosphodiesterase system in eleven patients with chronic renal disease. Glomerular filtration rate (+ 19%), effective renal plasma flow )+ 29%), sodium (+ 199%) and potassium (+ 40%) clearances were significantly increased. These effects were associated with a stimulation of the adenyl cyclase phosphodiesterase system demonstrated by an increase of cyclic adenosine 3'5'-monophosphate in plasma and urine. The results suggest that dopamine probably affects renal function by activating the adenyl cyclase phosphodiesterase system.

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The effect of a single, intravenously administered dose of glucagon on plasma cyclic adenoside monophosphate (cAMP) was studied in seven normal subjects, ten patients with chronic renal failure (CRF), and ten patients with terminal renal insufficiency (TRI) receiving long-term haemodialysis treatment (HD). Ten minutes following glucagon administration, uremic patients displayed a significantly (P less than 0.0001) greater increase in cAMP than control subjects. Glucose levels after glucagon administration did not differ significantly between the normal and uremic groups, and lipolysis was less pronounced in the uremic patients than in the controls (P less than 0.003). These results could not be attributed to differences in serum insulin response. The findings demonstrate differences in the hepatic adenylate cyclase and cAMP response between normal and uremic subjects. These alterations in cAMP responsiveness may play a role in the pathophysiology of the metabolic disturbances associated with uremia.

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